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Cited by 25Antifungal resistance and susceptibilityFungal Infections and StudiesFungal and yeast genetics research

Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris

Open access
Balakumar, Abishek, Das, Diprasom, Datta, Abhishek, Mishra, Abtar, Bryak, Garrett, Ganesh, Shrihari M., Netea, Mihai G., Kumar, Vinod +4 more·2024·PLOS Pathogens
DOI 10.1371/journal.ppat.1012699PMC PMC11507746

Published version of a preprint

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Abstract

Candida auris is an emerging multidrug-resistant fungal pathogen that preferentially colonizes and persists in skin tissue, yet the host immune factors that regulate the skin colonization of C . auris in vivo are unknown. In this study, we employed unbiased single-cell transcriptomics of murine skin infected with C . auris to understand the cell type-specific immune response to C . auris . C . auris skin infection results in the accumulation of immune cells such as neutrophils, inflammatory monocytes, macrophages, dendritic cells, T cells, and NK cells at the site of infection. We identified fibroblasts as a major non-immune cell accumulated in the C . auris infected skin tissue. The comprehensive single-cell profiling revealed the transcriptomic signatures in cytokines, chemokines, host receptors (TLRs, C-type lectin receptors, NOD receptors), antimicrobial peptides, and immune signaling pathways in individual immune and non-immune cells during C . auris skin infection. Our analysis revealed that C . auris infection upregulates the expression of the IL-1RN gene (encoding IL-1R antagonist protein) in different cell types. We found IL-1Ra produced by macrophages during C . auris skin infection decreases the killing activity of neutrophils. Furthermore, C . auris uses a unique cell wall mannan outer layer to evade IL-1R-signaling mediated host defense. Collectively, our single-cell RNA seq profiling identified the transcriptomic signatures in immune and non-immune cells during C . auris skin infection. Our results demonstrate the IL-1Ra and IL-1R-mediated immune evasion mechanisms employed by C . auris to persist in the skin. These results enhance our understanding of host defense and immune evasion mechanisms during C . auris skin infection and identify potential targets for novel antifungal therapeutics.

AI snapshot

Written from the paper’s full text.

TL;DR

Single-cell RNA sequencing of murine skin infected with *Candida auris* maps cell-type-specific antifungal immune responses and identifies fibroblast accumulation alongside innate and adaptive immune cell recruitment. The study further shows that *C. auris* induces macrophage-derived IL-1Ra, which suppresses neutrophil killing, and uses its outer mannan layer to evade IL-1R-mediated neutrophil recruitment and function.

Key findings

  • Unbiased scRNA-seq captured 70,350 cells, 30 clusters, and 35 distinct cell types (16 immune, 19 non-immune); infected skin showed accumulation of neutrophils (99.9%), macrophages (99.6%), inflammatory monocytes (93%), and fibroblast 3 (87.9%) among the reported cell-type percentages.
  • Myeloid subsets had extensive differential expression after infection, including neutrophils with 1,107 DEGs (1,105 upregulated, 2 downregulated) and macrophages with 1,340 DEGs (1,322 upregulated, 18 downregulated); upregulated genes included chemokines, PRRs, AMPs, nitric oxide metabolism genes, and acute-phase *Saa3*.
  • Lymphoid analysis showed IL-17 and IFNγ pathway involvement: *Il17a* and *Il17f* were mainly expressed in CD4+ Th cells and γδ T cells, while *Ifng* was increased in NK cells followed by CD4+ Th cells, CD8+ cells, and γδ T cells.
  • *C. auris*-infected skin had significantly higher IL-1Ra than uninfected and *C. albicans*-infected skin; recombinant IL-1Ra decreased neutrophil killing of *C. auris*, anti-IL-1Ra neutralizing antibody reduced skin fungal burden, macrophage depletion decreased IL-1Ra and fungal load, and the *pmr1Δ* mannan mutant showed altered IL-1R-dependent neutrophil recruitment and killing.

Methods

  • Mice (C57BL/6J and IL-1R1−/−) were infected intradermally with 1–2 × 10^6 *C. auris* yeast cells or PBS; skin was collected at 12 days post-infection for scRNA-seq using the 10x Genomics Chromium platform and Illumina NovaSeq 6000.
  • Bioinformatics used CellRanger v7.1.0 (mm10), Seurat v4, SoupX, SingleR with reference GSE181720, and edgeR pseudo-bulk differential expression with FDR < 5% and log2 fold change ≥ 2 or ≤ −2; KEGG pathway enrichment used clusterProfiler.
  • Functional validation included flow cytometry, IL-1Ra ELISA, neutrophil killing assays, anti-Ly6G neutrophil depletion, clodronate liposome macrophage depletion, IL-1Ra neutralization, CRISPR-generated *pmr1Δ* mutant infection, and bone marrow-derived macrophage stimulation.

Limitations

  • The paper states that IL-1Ra induction may differ between murine and human skin, that intraspecies variation in IL-1 regulation of innate immune responses may exist, and that future ex vivo human skin infection models are needed.
  • The paper states that future studies are needed to understand the roles of DCs, Th1 cells, NK cells, and fibroblasts, and the functional importance of IFNγ in *C. auris* skin infection.
  • Evident from the text: the scRNA-seq analysis was performed at a single 12-day post-infection time point in a murine intradermal model, so the transcriptomic snapshot may not capture earlier or later skin immune dynamics.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.ppat.1012699

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

43 of 63 cited sources checked · 14 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    C. auris preferentially colonizes and persists in human skin tissue.

    “Candida auris is an emerging multidrug-resistant fungal pathogen that preferentially colonizes and persists in skin tissue”
    • Also stated in: § Introduction · plain
      “C. auris preferentially colonizes the human skin, leading to nosocomial transmission and outbreaks of systemic fungal infections [4–6].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [4] X Huang, 2021, Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies, Cell Host Microbe source

      The Introduction reports that C. auris can colonize patients’ skin for months, and the Results show persistent residence deeper within mouse skin tissue. The Discussion describes a human skin-tissue reservoir as a possibility, not an established finding; the paper says deeper tissue colonization has not been tested in patients. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [5] PS Shastri, 2020, Candida auris candidaemia in an intensive care unit—Prospective observational study to evaluate epidemiology, risk factors, and outcome., J Crit Care source
    • cites [6] DM Proctor, 2023, One population, multiple lifestyles: Commensalism and pathogenesis in the human mycobiome, Cell Host Microbe source
  • Premisecitation

    The cell wall of C. auris is structurally and biologically unique compared to other Candida species, including C. albicans.

    “Recent evidence indicates that the cell wall of C. auris is structurally and biologically unique compared to other Candida species, including C. albicans [13].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] M Bruno, 2020, Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris., Nat Microbiol. source

      The Results sections on C. auris mannans and the host response describe distinctive mannan structures and different immune responses compared with C. albicans. But the comparison does not establish uniqueness relative to other Candida species generally, and the paper explicitly finds no structurally unique features in C. auris β-glucans. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    C. auris possesses a unique outer mannan layer compared to C. albicans.

    “C. auris possesses a unique outer mannan layer compared to C. albicans [13]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] M Bruno, 2020, Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris., Nat Microbiol. source
  • Premisecitation

    Growth kinetics was unaltered in C. auris pmr1Δ.

    “The growth kinetics was unaltered in C. auris pmr1Δ [34]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] MV Horton, 2021, Candida auris Cell Wall Mannosylation Contributes to Neutrophil Evasion through Pathways Divergent from Candida albicans and Candida glabrata, mSphere source
  • Premisecitation

    IL-1R signaling is critical for neutrophil function.

    “IL-1R signaling is critical for neutrophil function [26, 31, 32]”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [26] A Mantovani, 2019, Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity, Immunity source

      The Hemopoiesis, ageing and innate memory section (page unavailable) says IL-1 promotes neutrophil survival. The Gastrointestinal tract section (page unavailable) also reports IL-1 promoting neutrophil-mediated control of bacterial invasion in a colorectal-cancer study. These support a role for IL-1 signaling in particular neutrophil-related responses, but do not establish that IL-1R signaling is critical for neutrophil function generally. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [31] S Altmeier, 2016, IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa, PLoS Pathog. source

      The Results section on neutrophil recruitment (page unavailable) says IL-1R signaling was critical for the neutrophil response during oropharyngeal candidiasis in mice. The Discussion (page unavailable) specifies that the demonstrated effects concern neutrophil recruitment and production; it does not establish that IL-1R signaling is critical for neutrophil function generally or for neutrophils’ intrinsic activity. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [32] S Bellocchio, 2004, The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo, J Immunol source
  • Classified as probably not a substantial claim. 29
  • May combine two claims. 31

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    SingleR v2.0.0 was used for cell type annotation of the clusters using reference dataset GSE181720.

    “SingleR (v 2.0.0) package[55] was used for cell type annotation of the clusters using reference dataset GSE181720 [23].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [55] MD Robinson, 2010, edgeR: a Bioconductor package for differential expression analysis of digital gene expression data, Bioinformatics source

      The citation attached to SingleR identifies a package, but the Introduction identifies the cited paper’s package as edgeR, not SingleR. The reference dataset GSE181720 has a separate citation and is not attributed to this source. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [23] G Venugopal, 2022, In vivo transcriptional analysis of mice infected with Leishmania major unveils cellular heterogeneity and altered transcriptomic profiling at single-cell resolution, PLOS Neglected Tropical Diseases source

  • May combine two claims.

    Premisecitation

    C. auris can persist in skin tissues for several months and evade routine clinical surveillance.

    “C. auris can persist in skin tissues for several months and evade routine clinical surveillance [4, 8].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [4] X Huang, 2021, Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies, Cell Host Microbe source

      In Results (“Candida auris Persistently Colonizes Skin”), live C. auris was recovered from deeper mouse skin tissue for up to four months, after surface swabs had become negative. The paper uses those swabs to model clinical surveillance, but explicitly says deeper-tissue colonization has not been tested in human patients. Thus persistence that escapes surface swabbing is supported in mice, not established as evasion of routine clinical surveillance in humans. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [8] DM Proctor, 2021, Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility, Nature Medicine source

  • May combine two claims.

    Premisecitation

    C. auris not only colonizes the epidermis of the skin but also enters the deeper dermis.

    “Furthermore, unlike skin-tropic fungal pathogens such as Malassezia [7], C. auris not only colonizes the epidermis of the skin but also enters the deeper dermis, a phenomenon that was not observed previously [4].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] X Huang, 2021, Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies, Cell Host Microbe source

      The Results section (‘Candida auris Persistently Colonizes Skin’; page unavailable) reports C. auris on the skin surface and deeper within mouse skin tissue, including hair follicles. It does not identify the deeper site specifically as the dermis, and it says deeper-tissue colonization has not been examined in human patients. The claim therefore extends beyond what this murine study establishes. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The murine skin model is widely used to study disease pathogenesis and C. auris-host interactions.

    “In addition, understanding the skin immune responses against C. auris is critical, as the murine skin model is widely used to study disease pathogenesis and C. auris-host interactions [4, 16–20].”
    Quote in the paperNot a substantial claim4 of 6 sources checked
    • cites [4] X Huang, 2021, Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies, Cell Host Microbe source

      The Introduction says the authors developed a mouse model to examine C. auris skin colonization, and the Discussion says they used it to investigate host risk factors. But the Introduction also says no animal model had previously been developed for this purpose, so this paper does not support calling the model “widely used.” (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [16] S Seiser, 2024, Native human and mouse skin infection models to study Candida auris-host interactions, Microbes Infect source
    • cites [17] DJ Santana, 2023, A Candida auris-specific adhesin, Scf1, governs surface association, colonization, and virulence, Science source

      In “SCF1 promotes long-term colonization and virulence” (page unavailable), the paper uses in vivo murine skin to study C. auris colonization and potential interaction with host tissue. It does not establish that the murine skin model is widely used or use that model to study disease pathogenesis; its virulence experiments use intravenous infection instead. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [18] J Herrada, 2022, In Vivo Skin Colonization and Decolonization Models for Candida auris, Methods Mol Biol source
    • cites [19] G Bryak, 2024, Yeast and filamentous Candida auris stimulate distinct immune responses in the skin, mSphere source
    • cites [20] A Datta, 2023, Differential skin immune responses in mice intradermally infected with Candida auris and Candida albicans., Microbiol Spectr. source

  • May combine two claims.

    Premisecitation

    The outer cell wall mannan layer in C. auris is highly enriched in β-1,2-linkages and contains two unique Mα1-phosphate side chains not found in other Candida species.

    “The outer cell wall mannan layer in C. auris is highly enriched in β-1,2-linkages and contains two unique Mα1-phosphate side chains not found in other Candida species [13].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] M Bruno, 2020, Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris., Nat Microbiol. source

      The Results section, “Unique structure of C. auris mannans” (page not available), reports β−1,2-mannose linkages in varying amounts and two distinct M-α−1-phosphate side chains described as a unique structural feature. It does not say the mannans are highly enriched in β−1,2 linkages, and its comparison is with C. albicans rather than all other Candida species. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida auris is an emerging multidrug-resistant fungal pathogen.

    “Candida auris is an emerging multidrug-resistant fungal pathogen that preferentially colonizes and persists in skin tissue”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [1] S Ahmad, 2021, Candida auris: Epidemiology, Diagnosis, Pathogenesis, Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in Healthcare Facilities., Microorganisms. source
    • cites [2] WHO fungal priority pathogens list to guide research,, 2022

      Not checked in the free run.

    • cites [3] SS Kadri, 2020, Key Takeaways From the U.S. CDC’s 2019 Antibiotic Resistance Threats Report for Frontline Providers., Crit Care Med source
    • Rests on an assumption: The majority of C. auris isolates exhibit resistance to several FDA-approved antifungal drugs.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    C. auris differentially stimulates cytokine production in peripheral blood mononuclear cells and has a more potent binding to IgG than C. albicans.

    “C. auris differentially stimulates cytokine production in peripheral blood mononuclear cells and has a more potent binding to IgG than C. albicans [14, 15].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [14] Y Wang, 2022, Innate immune responses against the fungal pathogen Candida auris., Nat Commun. source

      The Results section on PBMC responses reports that C. auris sometimes elicited more cytokine production than C. albicans, although most tests showed similar responses. Our copy does not establish stronger IgG binding by C. auris than by C. albicans; IgG binding appears in the title of a work listed in the References, without that comparison. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [15] L Yan, 2020, Unique Cell Surface Mannan of Yeast Pathogen Candida auris with Selective Binding to IgG, ACS Infect Dis source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fungal cell wall components represent the predominant pathogen-associated molecular patterns (PAMPs) directly interacting with the host to orchestrate the antifungal immune response.

    “The fungal cell wall components represent the predominant pathogen-associated molecular patterns (PAMPs) directly interacting with the host to orchestrate the antifungal immune response [12].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] B Briard, 2021, Fungal cell wall components modulate our immune system, Cell Surf source

  • May combine two claims.

    Premisecitation

    C. auris skin infection leads to fungal dissemination, suggesting skin infection is a source of invasive fungal infection.

    “Recent evidence from our laboratory indicates that C. auris skin infection leads to fungal dissemination, suggesting skin infection is a source of invasive fungal infection [9].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] KA Towns, 2024, Intradermal infection and dissemination of Candida auris in immunocompetent and immunocompromised mouse models., Microbiol Spectr. source

      The OBSERVATION section reports dissemination from intradermally infected mouse skin to internal organs and describes skin infection as a potential source of invasive infection. But it also reports no detectable dissemination after epicutaneous infection, so the unqualified claim about C. auris skin infection is broader than the evidence. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    C. auris possesses a unique cell wall, adhesin proteins, and colonizing factors to thrive in the skin.

    “C. auris possesses a unique cell wall, adhesin proteins, and colonizing factors to thrive in the skin [13, 17, 36]”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [13] M Bruno, 2020, Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris., Nat Microbiol. source

      The Results section, “Unique structure of C. auris mannans,” identifies distinctive cell-wall features, and the introductory passage labeled Abstract says C. auris strongly colonizes skin. Neither passage identifies adhesin proteins or specific colonizing factors that enable it to thrive on skin, or links the described cell-wall features to skin colonization. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [17] DJ Santana, 2023, A Candida auris-specific adhesin, Scf1, governs surface association, colonization, and virulence, Science source

      The Abstract and Discussion (page not provided) describe C. auris adhesins, including SCF1, that contribute to skin colonization. Our copy does not establish that C. auris has a unique cell wall, so that part of the claim is unsupported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [36] A Balakumar, 2024, The adhesin SCF1 mediates Candida auris colonization, Trends in Microbiology source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    IL-17-producing T cells are critical for skin defense against C. auris.

    “Recent studies suggest that IL-17-producing T cells are critical for skin defense against C. auris [4]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] X Huang, 2021, Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies, Cell Host Microbe source

      The Results section reports greater C. auris skin colonization in mice lacking T cells and suggests that IL-17-producing T cells contribute to its control. But it also identifies IL-17-producing innate lymphoid cells as protective and says they can partially compensate for deficient IL-17 production by another cell population; the murine findings do not establish that T cells alone are critical for skin defense. Page numbers were not provided in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    IL-1R signaling is critical for neutrophil recruitment and function and plays an important role in host defense against C. albicans in oral mucosa and systemic infection.

    “IL-1R signaling is critical for neutrophil recruitment and function and plays an important role in the host defense against C. albicans in oral mucosa and systemic infection [31, 32]”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [31] S Altmeier, 2016, IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa, PLoS Pathog. source

      The Results and Discussion show that IL-1R signaling promotes neutrophil recruitment and fungal control in a mouse model of oral candidiasis. The Discussion also reports previous evidence for an IL-1R role in systemic candidiasis, but this paper does not establish that IL-1R regulates neutrophil function during systemic infection; it says the protective mechanism was not addressed in most of those studies. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [32] S Bellocchio, 2004, The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo, J Immunol source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The Il1rn gene encodes four isoforms of IL-1R antagonist (IL-1Ra), which regulates inflammatory signaling of the IL-1 pathway by competing with IL-1α and IL-1β in IL-1R activation.

    “The Il1rn gene encodes four isoforms of IL-1R antagonist (IL-1Ra), which regulates the inflammatory signaling of the IL-1 pathway by competing with IL-1α and IL-1β in IL-1R activation”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [26] A Mantovani, 2019, Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity, Immunity source

      The section on receptors and negative regulation identifies IL-1Ra as a receptor antagonist that binds IL-1R1; it also says IL-1α and IL-1β use that receptor to signal. This supports the claim about antagonizing their signaling, but our copy does not state that the Il1rn gene encodes four IL-1Ra isoforms. Page numbers were not available in the indexed passages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [27] DB Carter, 1990, Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein, Nature source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PRRs in myeloid cells facilitate fungal recognition in the host.

    “The PRRs in the myeloid cells facilitate fungal recognition in the host [24, 38]”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [24] MG Netea, 2015, Immune defence against Candida fungal infections, Nature Reviews Immunology source
    • cites [38] HR Conti, 2015, IL-17–Mediated Immunity to the Opportunistic Fungal Pathogen Candida albicans, The Journal of Immunology source

      Section 2, “Pattern Recognition of Candida albicans” (page unavailable), says PRRs, particularly C-type lectin receptors, recognize Candida cell-wall components. Section 6A discusses Dectin-1 responses in antigen-presenting cells, but the cited passages do not specifically establish the claim about PRRs in myeloid cells. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Fungal PAMPs modulate the host response.

    “fungal PAMPs modulate the host response [12]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] B Briard, 2021, Fungal cell wall components modulate our immune system, Cell Surf source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    IL-1Ra induction may differ between murine and human skin, and intraspecies variation in the IL-1 regulation of innate immune response may exist.

    “IL-1Ra induction may differ between the murine and human in the skin, and intraspecies variation in the IL-1 regulation of innate immune response may exist [46]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [46] K Sakamoto, 2022, Flow cytometry analysis of the subpopulations of mouse keratinocytes and skin immune cells., STAR Protocols source

      The Expected outcomes section describes flow-cytometry gating for mouse skin immune cells, and the Limitations section discusses differences between mouse strains in NK1.1 expression. Neither addresses IL-1Ra induction in murine versus human skin or intraspecies variation in IL-1 regulation. Searches for IL-1Ra and interleukin-1 receptor antagonist found no relevant passage in our copy; page numbers were unavailable. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The IL-17 pathway plays a critical role in antifungal host defense, including C. auris.

    “the IL-17 pathway, which plays a critical role in antifungal host defense, including C. auris [4, 39]”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [4] X Huang, 2021, Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies, Cell Host Microbe source
    • cites [39] S Kagami, 2010, IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans, Journal of immunology (Baltimore, Md: 1950). source

      The Discussion (page unavailable) reports that IL-17A is a key mediator of skin defense against C. albicans in mice. The paper does not address C. auris, so it does not support extending that finding to this species. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The quality of cDNA and library was examined by a Bioanalyzer at each step.

    “At each step, the quality of cDNA and library was examined by a Bioanalyzer [48, 49].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [48] GXY Zheng, 2017, Massively parallel digital transcriptional profiling of single cells, Nature Communications source

      The Methods section on GemCode sequencing-library construction mentions library quantification by PCR, but the passages found do not say that cDNA or library quality was examined with a Bioanalyzer at each step. Searches for Bioanalyzer, Agilent, and library quality assessment found no passage addressing that procedure; page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [49] T Stuart, 2019, Comprehensive Integration of Single-Cell Data, Cell source

      The STAR Methods section mentions cDNA amplification and RNA-seq library preparation but does not say their quality was checked with a Bioanalyzer at each step. Searches for “Bioanalyzer” and cDNA/library quality control found no passage addressing that procedure. (LLM, conf=0.73)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Intradermal infection of mice leads to dissemination of fungi to kidneys and spleen.

    “Although the intradermal infection of mice leads to the dissemination of fungi to kidneys and spleen [9]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] KA Towns, 2024, Intradermal infection and dissemination of Candida auris in immunocompetent and immunocompromised mouse models., Microbiol Spectr. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Epicutaneous and intradermal infection elicits different immune responses.

    “epicutaneous and intradermal infection elicits different immune responses [41, 42]”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [41] SW Kashem, 2015, Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation, Immunity source
    • cites [42] Guerrero-Juarez CF Zhang L-j, 2015, Dermal adipocytes protect against invasive Staphylococcus aureus skin infection, Science source

      The skin-infection passages (indexed under Abstract; page unavailable) describe dermal adipocyte expansion and cathelicidin production after S. aureus infection, including at a site injected with bacteria. Searches for epicutaneous infection and for a comparison with intradermal infection found no passage comparing immune responses by infection route. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    IL-17 (Th17) but not IL-12 (Th1) is critical for host defense against Candida albicans in the skin tissue.

    “Previous findings indicate that IL-17 (Th17) but not IL-12 (Th1) is critical for host defense against Candida albicans in the skin tissue [40]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [40] JL Linehan, 2018, Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair, Cell source

      The Results section on S. epidermidis-induced skin T cells discusses IL-17A-producing cells, but not defense against Candida albicans. Searches for Candida and for the IL-17-versus-IL-12 comparison found no passage in our copy addressing that claim. (LLM, conf=0.75)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    SoupX version 1.5.2 was used to identify and remove ambient RNA background noise from the scRNA-seq data.

    “To address the ambient RNA contamination SoupX version 1.5.2[54] was utilized to identify and remove ambient RNA background noise from the data.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [54] D Aran, 2019, Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage, Nature Immunology source

      The Results section describes SingleR for cell-type annotation, while Online Methods (Drop-seq and data analysis; page unavailable) describes processing and clustering with Seurat. Searches for SoupX, version 1.5.2, and ambient RNA correction found no passage addressing the claimed use of SoupX. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Il1a, Il1b, and Il1rn were highly expressed in macrophages, whereas Il1b and Il1rn were highly expressed in monocytes and dendritic cells 1.

    “Il1a, Il1b, and Il1rn were highly expressed in macrophages, whereas Il1b and Il1rn were highly expressed in monocytes and dendritic cells 1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among the top 10 DEGs in myeloid cells, chemokine genes such as Ccl4 and Cxcl3 in neutrophils, Cxcl9 and Ccl5 in inflammatory monocytes, and Cxcr2 in dermal dendritic cells were significantly upregulated in the C. auris infected group.

    “Among the top 10 DEGs in myeloid cells, chemokine genes such as Ccl4 and Cxcl3 in neutrophils, Cxcl9 and Ccl5 in inflammatory monocytes, and Cxcr2 in dermal dendritic cells were significantly upregulated in the C. auris infected group (Figure 2A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among antimicrobial peptides, Lcn2, S100a8, and S100a9 were highly expressed in neutrophils, and Ang was selectively expressed in resident macrophages.

    “Among the AMPs, the Lcn2, S100a8, and S100a9 were highly expressed in neutrophils, and the Ang was selectively expressed in the resident macrophages (Figure 2D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    C. auris infection induced differential expression of genes in myeloid subsets, with 1107 genes in neutrophils, 299 in inflammatory monocytes, 1340 in macrophages, 357 in resident macrophages, 454 in dendritic cell 1, 265 in dendritic cell 2, and 262 in dermal dendritic cells.

    “In neutrophils, 1107 genes (1105 upregulated and 2 downregulated), inflammatory monocytes, 299 genes (217 upregulated and 82 downregulated), macrophages, 1340 genes (1322 upregulated and 18 downregulated), resident macrophages, 357 genes (143 upregulated and 214 downregulated), dendritic cell 1, 454 genes (260 upregulated and 194 downregulated), dendritic cell 2, 265 genes (244 upregulated and 21”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The analysis identified percentages of immune and non-immune cells accumulated at the site of infection, including neutrophils 99.9%, basophils 80.5%, inflammatory monocytes 93%, macrophages 99.6%, dendritic cell 1 83.3%, dendritic cell 2 90.9%, helper T cell 96.4%, cytotoxic T cells 81%, Tregs 84.9%, NK cells 90.9%, B-cells 64.7%, proliferating T cells 66.5%, resident macrophages 58.9%, dermal DC

    “Our analysis identified the percentage of immune and non-immune cells accumulated at the site of infection; (neutrophils - 99.9%, basophils - 80.5%, inflammatory monocytes - 93%, macrophages - 99.6%, dendritic cell 1 - 83.3%, dendritic cell 2 - 90.9%, helper T cell - 96.4%, cytotoxic T cells - 81%, Tregs - 84.9%, NK cells - 90.9%, B-cells - 64.7%, proliferating T cells - 66.5%, resident macrophage”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After cell-type annotation, 16 cell types were identified as immune cells and the remaining 19 as non-immune cells.

    “After cell-type annotation, we identified 16 cell types as immune cells and the rest 19 as non-immune cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Saa3 is the highest upregulated gene in fibroblast 3, and Saa1 and Saa3 were highly upregulated in fibroblast 1.

    “The serum amyloid protein Saa3 is the highest upregulated gene in fibroblast 3, and the Saa1 and Saa3 were highly upregulated in fibroblast 1 (Figure. 4A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among DEGs in fibroblast subsets, 370 genes in fibroblast 1, 68 genes in fibroblast 2, 389 genes in fibroblast 3, and 9 genes in fibroblast 4 were regulated upon C. auris infection.

    “Among the DEGs in fibroblast subsets, 370 genes in fibroblast 1 (150 upregulated and 220 downregulated), 68 genes in fibroblast 2 (12 upregulated and 56 downregulated), 389 genes in fibroblast 3 (294 upregulated and 95 downregulated) and 9 genes in fibroblast 4 (1 upregulated and 8 downregulated) were regulated upon C. auris infection.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    After quality filtering by removing noise and batch effects, the scRNA-seq data comprised 70,350 cells.

    “After quality filtering by removing noise and batch effects, our data comprised 70,350 cells (Table S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    C. auris uses a unique cell wall mannan outer layer to evade IL-1R-signaling mediated host defense and persist in skin tissue.

    “Furthermore, C. auris uses a unique cell wall mannan outer layer to evade IL-1R-signaling mediated host defense.”
    • Also stated in: § Introduction · plain
      “Furthermore, C. auris evades IL-1R-mediated host defense through a unique outer mannan layer to persist the skin tissue.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Secreted IL-1Ra during C. auris skin infection decreases neutrophil function and potentially favors fungal growth in the skin tissue in vivo.

    “These findings indicate that the secreted IL-1Ra during C. auris skin infection decreases neutrophil function and potentially favors fungal growth in the skin tissue in vivo”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fibroblasts and keratinocytes are known to express intracellular isoforms of IL-1Ra.

    “fibroblasts and keratinocytes, that are known to express intracellular isoforms of IL-1Ra [28, 29]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] P Martin, 2020, Intracellular IL-1 Receptor Antagonist Isoform 1 Released from Keratinocytes upon Cell Death Acts as an Inhibitor for the Alarmin IL-1α, The Journal of Immunology source
    • cites [29] S Kanangat, 2006, Novel Functions of Intracellular IL-1ra in Human Dermal Fibroblasts: Implications in the Pathogenesis of Fibrosis, Journal of Investigative Dermatology source

  • May combine two claims.

    Interpretationown data

    IL-1Ra produced by macrophages during C. auris skin infection decreases neutrophil function, which is important for antifungal host defense against this emerging skin tropic fungal pathogen.

    “Collectively, our results indicate that the IL-1Ra produced by macrophages during C. auris skin infection decreases the neutrophil function, which is important for antifungal host defense against this emerging skin tropic fungal pathogen”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The deletion of PMR1 in C. auris AR0387 was confirmed using Sanger sequencing.

    “The deletion of PMR1 was confirmed using Sanger sequencing (Table S7).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    C. auris induces IL-1Ra in macrophages to decrease neutrophil function and evades IL-1R-mediated immune defense against C. auris.

    “Our findings demonstrate that C. auris induces IL-1Ra in macrophages to decrease neutrophil function and evades IL-1R-mediated immune defense against C. auris”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Depletion of macrophages, but not neutrophils, significantly decreased IL-1Ra concentrations in the skin tissue of mice infected with C. auris, suggesting the macrophage as the major source of IL-1Ra during C. auris skin infection.

    “We identified that the depletion of macrophages, but not neutrophils, significantly decreased IL-1Ra concentrations in the skin tissue of mice infected with C. auris, suggesting the macrophage as the major source of IL-1Ra during C. auris skin infection”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Only samples with more than 85% cell viability and with less debris and aggregates were used for single-cell partitioning and RNA library preparation.

    “Samples with more than 85% cell viability and less debris and aggregates were enumerated using a hemocytometer and adjusted to ~10,000,000/mL for further Single-cell partition and RNA library preparation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    During Staphylococcus aureus skin infection, dermal fibroblasts differentiate into adipocytes and produce AMP, mainly CAMP, for host defense.

    “During Staphylococcus aureus skin infection, the dermal fibroblasts differentiate into adipocytes and produce AMP, mainly CAMP, for host defense [43]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] H Weerasinghe, 2023, Candida auris uses metabolic strategies to escape and kill macrophages while avoiding robust activation of the NLRP3 inflammasome response, Cell Rep source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Two technical replicates were processed for each sample in the scRNA-seq experiment.

    “Two technical replicates for each sample were processed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    C. albicans and C. auris infection induces IL-1Ra in macrophages and decreases the killing activity of neutrophils to different host niches, including the kidney and skin, respectively.

    “Our results, along with others [35], suggest that C. albicans and C. auris infection induces IL-1Ra in macrophages and decreases the killing activity of neutrophils to different host niches, including the kidney and skin, respectively”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] HTT Gander-Bui, 2023, Targeted removal of macrophage-secreted interleukin-1 receptor antagonist protects against lethal Candida albicans sepsis, Immunity source

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Depletion of neutrophils and macrophages was assessed by flow cytometry.

    “Depletion of neutrophils and macrophages was assessed by flow cytometry.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    scRNA seq revealed transcriptome changes in different immune and non-immune cell types during C. auris infection in mice skin tissue in vivo and identified previously unknown immune and non-immune cell type-specific host responses against C. auris skin infection.

    “Collectively, our scRNA seq revealed the transcriptome changes in different immune and non-immune cell types during C. auris infection in mice skin tissue in vivo and identified the previously unknown immune and non-immune cell type-specific host responses against C. auris skin infection”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Bone marrow-derived macrophages were confirmed for CD11b+ MHCII+ by flow cytometry after 5-8 days of culture.

    “After 5 –8 days, the adherent cells were separated, washed, and confirmed for CD11b+ MHCII+ by flow cytometry.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Unbiased transcriptomics identified the potential contribution of the IFNγ pathway in lymphoid cells and the involvement of non-immune cells in skin defense against C. auris.

    “our unbiased transcriptomics identified the potential contribution of the IFNγ pathway in lymphoid cells and the involvement of non-immune cells in skin defense against C. auris”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Differentially expressed genes were identified based on FDR ≤ 0.05 and Log2FC ≥ 2 or ≤ −2 between infected and uninfected conditions for each cell type.

    “Then we applied statistical models to identify genes that were significantly differentially expressed based on FDR ≤ 0.05 and Log2FC ≥ 2 or ≤ −2 between infected and uninfected conditions for each cell type.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    C. auris was less potent in activating IL-1β than C. albicans, evading macrophages through metabolic adaptation.

    “A recent study demonstrated that C. auris was less potent in activating IL-1β than C. albicans, evading macrophages through metabolic adaptation [44]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] P Luz-Crawford, 2016, Mesenchymal Stem Cell-Derived Interleukin 1 Receptor Antagonist Promotes Macrophage Polarization and Inhibits B Cell Differentiation, Stem Cells source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent study on C. albicans using a systemic mouse model of infection revealed the role of secreted IL-1Ra by splenic macrophages limits neutrophil activity in kidneys, contributing to immune evasion of fungi.

    “A recent study on C. albicans using a systemic mouse model of infection revealed the role of secreted IL-1Ra by splenic macrophages limits the neutrophil activity in kidneys, contributing to the immune evasion of fungi [35]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] HTT Gander-Bui, 2023, Targeted removal of macrophage-secreted interleukin-1 receptor antagonist protects against lethal Candida albicans sepsis, Immunity source

  • May combine two claims.

    Interpretationown data

    Non-immune cells exhibit an active role in skin defense against C. auris through AMPs and by secreting soluble factors that assist in recruiting neutrophils to the site of infection.

    “These findings suggest that non-immune cells exhibit an active role in skin defense against C. auris through AMPs and by secreting soluble factors that assist in recruiting neutrophils to the site of infection”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    IL-1Ra-mediated immune evasion mechanisms employed by C. auris modulate macrophages and persist in the skin.

    “Our findings indicate the IL-1Ra-mediated immune evasion mechanisms employed by C. auris to modulate macrophages and persist in the skin”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Cells with fewer than 300 or more than 7500 unique feature counts or more than 20% mitochondrial reads were excluded from the scRNA-seq analysis.

    “Cells with fewer than 300 or more than 7500 unique feature counts or more than 20% mitochondrial reads were excluded.”
    Quote in the paperNot a substantial claim
52 of 52

  • The paper relies on this without support.

    Host immune factors that regulate skin colonization of C. auris in vivo are unknown.

    “yet the host immune factors that regulate the skin colonization of C. auris in vivo are unknown.”

  • The paper relies on this without support.

    Almost nothing is known regarding skin immune responses against C. auris.

    “to date, almost nothing is known regarding the skin immune responses against C. auris.”

  • The paper relies on this without support.

    Classical population-based gene expression studies using in-vitro differentiated immune cells and mouse models of systemic infection do not completely represent host defense mechanisms against skin infection in vivo.

    “Furthermore, classical population-based gene expression studies using in-vitro differentiated immune cells and mouse models of systemic infection do not completely represent the host defense mechanisms against skin infection in vivo.”

  • The paper relies on this without support.

    A closer look into cell type-specific host responses requires single-cell resolution to encompass all cell types involved in host defense against C. auris skin infection in vivo.

    “A closer look into cell type-specific host responses requires single-cell resolution to encompass all cell types, including immune and non-immune cells involved in host defense against C. auris skin infection in vivo.”

  • The paper relies on this without support.

    The majority of C. auris isolates exhibit resistance to several FDA-approved antifungal drugs.

    “Given that the majority of C. auris isolates exhibit resistance to several FDA-approved antifungal drugs, a deeper understanding of C. auris-host interactions is critical to understanding the pathogenesis and developing potential new host-directed therapeutic approaches to prevent and treat this newly emerging skin tropic fungal pathogen.”

  • The authors state this as an assumption.

    The role of IL-1Ra in host defense against C. auris skin infection is unknown.

    “the role of IL-1Ra in host defense against C. auris skin infection is unknown”

  • The authors state this as an assumption.

    The role of IL-1R signaling in host defense against C. auris skin infection is unknown.

    “the role of IL-1R signaling in host defense against C. auris skin infection is unknown”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • IL-17 and dermal fibroblasts play a critical role in skin defense during C. auris infection.

    “IL-17 and dermal fibroblasts play a critical role in skin defense during C. auris infection [6,16].”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [16]

    The Discussion describes IL-17-producing T cells as critical for skin defense against C. auris. The Results and Discussion identify fibroblast responses that could contribute to defense, but call for future studies of their role; they do not establish that dermal fibroblasts are critical. Page numbers are not provided in our copy's passages. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • C. auris uses a two-tiered evasion strategy: it masks immunogenic β-glucan through mannosylation to avoid neutrophil recognition and simultaneously induces macrophage-derived IL-1Ra to suppress IL-1R-dependent neutrophil recruitment and activation.

    “Together, these findings uncover a two-tiered evasion strategy: C. auris masks immunogenic β-glucan through mannosylation to avoid neutrophil recognition and simultaneously induces macrophage-derived IL-1Ra to suppress IL-1R-dependent neutrophil recruitment and activation.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [86]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Excessive IL-1Ra dampens protective neutrophil responses and favors fungal growth in the skin.

    “Exogenous IL-1Ra decreased the killing capacity of neutrophils ex vivo against C. auris, while IL-1Ra neutralization in C. auris-infected mice in vivo significantly reduced cutaneous fungal burden, demonstrating that excessive IL-1Ra dampens protective neutrophil responses and favors fungal growth in the skin.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [86]

    The Results section reports that recombinant IL-1Ra reduced neutrophil killing of C. auris ex vivo and that IL-1Ra neutralization reduced skin fungal burden in infected mice. It concludes that IL-1Ra decreases neutrophil function but says it *potentially* favors fungal growth in vivo; the citing sentence presents that last inference as demonstrated. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • IL-1R deficiency impairs neutrophil recruitment even against the pmr1Δ mutant strain, confirming the requirement of IL-1 signaling for anti-C. auris antifungal immunity in the skin.

    “In turn, IL-1R deficiency impaired neutrophil recruitment even against the pmr1Δ mutant strain, confirming the requirement of IL-1 signaling for anti-C. auris antifungal immunity in the skin.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [86]

    The Results section reports significantly decreased neutrophil recruitment in IL-1R-deficient mice infected with the pmr1Δ mutant. But it also reports no significant recruitment difference after infection with wild-type C. auris, so the unqualified claim that IL-1 signaling is required for skin immunity overstates this finding. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Skin fibroblast subsets express a broad array of cytokines, chemokines, PRRs, and AMPs in response to C. auris.

    “Skin fibroblast subsets also expressed a broad array of cytokines, chemokines, PRRs, and AMPs in response to C. auris, including Il33, Csf1, Tgfb2, Ccl2, Ccl7, Ccl11, Cxcl1, Cxcl5, Cxcl9, Cxcl10, Cxcl12, Cxcl14, Clec3b, Clec11a, Nod1, Mrc2, Lgals1, Lgals9, Lman1, Lnc2, Adm and Ang [86].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [86]

    The Results section on fibroblast transcriptomic signatures (Figure 4C–D; page not provided) reports cytokines, chemokines, fungal-recognizing receptors, and antimicrobial peptides in fibroblast subsets during C. auris skin infection, supporting the main claim and most listed genes. The cited fibroblast passage specifies Nod2, not Nod1, and Lcn2, not the citing sentence’s Lnc2; the paper reports Nod1 in myeloid cells instead. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting C. auris strain identifier

    Minor

    The results identify AR0285 as one of the four strains tested for IL-1Ra induction, but the fungal-culture methods list AR0385 instead and do not list AR0285.

  • IL-17 expression described as both selective and shared

    Minor

    One passage says Il17a and Il17f were selectively expressed in γδ T cells; a later passage says both were mainly expressed in CD4+ Th cells as well as γδ T cells.

2 of 2

Cites

Flagged first, then by citations

1 of the 66 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. WHO fungal priority pathogens list to guide research,, 2022, development and public health action

Cited by

Sorted by citations

Related

Authors
Balakumar, A., Das, D., Datta, A., Mishra, A., Bryak, G., Ganesh, S. M., Netea, M. G., Kumar, V., Lionakis, M. S., Arora, D., Thimmapuram, J., & Thangamani, S.
Affiliations
  • Purdue University West Lafayette (US)
  • University of Bonn (DE)
  • Radboud University Medical Center (NL)
  • National Institutes of Health (US)
Corresponding author
Thangamani, Shankar
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2024-11-13
Volume
20
Issue
11
Pages
e1012699
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1012699
PMC
PMC11507746
OpenAlex
W4404306630
Cited by
25
References
66
Citations by year
2026: 16 · 2025: 8 · 2024: 1
FWCI
7.88
Type
journal article
Language
en
Update notices
new_version (2024-11-25)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by-nc-sa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-sa)
  • Radboud Repository (Radboud University) (submittedVersion, cc-by-nc-sa)
  • Radboud Repository (Radboud University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (1R01AI177604, ZIA AI001175)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida auris, skin colonization, antifungal immunity, interleukin-1 receptor antagonist, immune evasion, macrophages, neutrophils, fibroblasts, TLRs, C-type lectin receptors, antimicrobial peptides, host-pathogen interaction, multidrug-resistant fungi

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-20.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-20.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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