CoChat
Sign Up
Cited by 30Antifungal resistance and susceptibilityFungal Infections and StudiesNail Diseases and Treatments

Differential skin immune responses in mice intradermally infected with Candida auris and Candida albicans

Open access
Datta, Abhishek, Das, Diprasom, Nett, Jeniel E., Vyas, Jatin M., Lionakis, Michail S., Thangamani, Shankar·2023·Microbiology Spectrum
DOI 10.1128/spectrum.02215-23PMC PMC10848846
Open this paper in CoChat — free account

Abstract

Candida auris , an emerging multi-drug-resistant fungal pathogen, uniquely colonizes the human skin long term, leading to subsequent development of life-threatening invasive infections in humans. The factors regulating skin colonization of C. auris are not well understood. In this study, we established an intradermal mouse model of C. auris infection to define the innate and adaptive immune response to this emerging pathogen and compare it to Candida albicans . Our results indicate that compared to C. albicans -infected mice, C. auris -infected mouse skin tissue had significantly higher fungal load after 3 and 14 days post-infection. C. auris infection was associated with a significantly decreased accumulation of CD11b+ Ly6G+ neutrophils and increased numbers of CD11b+ Ly6 C hi inflammatory monocytes and CD11b+ CD207+ Langerhans cells at the site of infection. Furthermore, a significant decrease in the absolute numbers of type 3 innate lymphoid cells and Th17 cells was observed in C. auris -infected skin tissue. Taken together, our findings indicate that the skin immune responses are different between C. auris - and C. albicans -infected mice. The increased fungal load observed in C. auris -infected mouse skin tissue is associated with less potent innate and adaptive immune responses induced by this emerging pathogen relative to C. albicans . IMPORTANCE: Candida auris is a globally emerging fungal pathogen that transmits among individuals in hospitals and nursing home residents. Unlike other Candida species, C. auris predominantly colonizes and persists in skin tissue, resulting in outbreaks of nosocomial infections. Understanding the factors that regulate C. auris skin colonization is critical to develop novel preventive and therapeutic approaches against this emerging pathogen. We established a model of intradermal C. auris inoculation in mice and found that mice infected with C. auris elicit less potent innate and adaptive immune responses in the infected skin compared to C. albicans . These findings help explain the clinical observation of persistent C. auris colonization in skin tissue.

AI snapshot

Written from the paper’s full text.

TL;DR

In an intradermal mouse model, C. auris produced higher skin fungal burdens and less potent innate/adaptive immune responses than C. albicans. This included fewer neutrophils and reduced type 3/Th17-associated cells, which may help explain persistent C. auris skin colonization.

Key findings

  • C. auris-infected skin had significantly higher fungal load than C. albicans at day 3 (7.51 ± 0.70 vs. ~5.97 ± 0.57 log10 CFU/g) and day 14 (5.47 ± 0.51 vs. 2.74 ± 0.23 log10 CFU/g); at day 14, detectable colonies were present in 6/7 C. auris-infected mice vs. 3/7 C. albicans-infected mice, with >80% C. auris persistence at 2 weeks.
  • Compared with C. albicans, C. auris infection was associated with significantly decreased CD11b+ Ly6G+ neutrophils and increased CD11b+ Ly6Chi inflammatory monocytes and CD11b+ CD207+ Langerhans cells at day 3 post-infection.
  • At day 14, C. auris infection was associated with significantly decreased total ILCs, IL-17A+ ILCs, and IL-17F+ ILCs, as well as decreased TCRβ+ IL-17A+, TCRβ+ IL-22+, CD4+ IL-17A+, CD4+ IL-17F+, and CD4+ IL-22+ T cells compared with C. albicans.
  • No significant fungal-load differences were observed among four C. auris clades, but CD11b+ CD207+ Langerhans cells and IL-17A+/IL-17F+ ILCs differed significantly among clades; neutrophils, Ly6Chi monocytes, and IL-17+ T cells did not.

Methods

  • Six- to eight-week-old C57BL/6J mice of both sexes were shaved/depilated and injected intradermally with C. albicans SC5314, C. auris isolates AR0381, AR0383, AR0385, or AR0387, or PBS; fungal burden was measured at days 3 and 14 by plating skin homogenates on YPD/CHROMagar.
  • Immune cells from whole skin were isolated by enzymatic digestion, stained for surface and intracellular markers, and analyzed by flow cytometry to quantify phagocytes, antigen-presenting cells, ILCs, and T-cell subsets.
  • Data are mean ± SEM; statistical analysis used Mann-Whitney U tests or Kruskal-Wallis tests followed by Dunn’s multiple comparisons, with P ≤ 0.05 considered significant.

Limitations

  • The paper has no dedicated limitations section; the discussion states that future studies are required to understand fungal factors driving differences among C. auris clades and the genetic/host factors underlying differential immune responses.
  • Evident from the text: findings are from an intradermal mouse model rather than natural epicutaneous colonization, and the authors note that route of infection may affect clade-specific fungal loads and invasion/localization.
  • Evident from the text: there is a dose inconsistency between Methods (1×–2×10^7 CFU/mouse) and Results (1–2×10^6 CFU/mouse), and the immune analyses are quantitative/associative rather than mechanistic.

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

Integrity signals

Registry

Crossref · 10.1128/spectrum.02215-23

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

38 of 47 cited sources checked · 16 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    C. auris was detected in mouse skin tissues 4 months after epicutaneous inoculation, indicating persistent deep skin colonization.

    “Recent findings indicate that C. auris was detected in the skin tissues of mice even after 4 months of initial epicutaneous inoculation, indicative of the persistent colonization in the deep skin tissue, which may evade routine clinical surveillance (4).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source
  • Premisecitation

    IL-17- and IL-22-producing TCRβ+ cells are important for host defense against fungal pathogens.

    “However, compared to C. albicans-infected mice, C. auris skin infection induces a significantly decreased number of IL-17- and IL-22-producing TCRβ+ cells that are important for host defense against fungal pathogens.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Results section reports that IL-17A/IL-17F produced in part by αβ T cells contributes to control of C. auris skin colonization. But the same section finds IL-22 dispensable for that control, so it does not support describing IL-22-producing cells as important for this defense. (LLM, conf=0.89)

      Experimental — accuracy not yet measured
    • cites [18] Kagami S, Rizzo HL, Kurtz SE, Miller LS, Blauvelt A. 2010. IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J Immunol 185: 5453– 5462. doi: 10.4049/jimmunol.1001153 20921529 PMC3076054 source

      The Discussion reports that IL-17A is important for defense against cutaneous C. albicans, and that CD3+ T cells produce it. But it says IL-22 is not required in this model: IL-22-deficient mice had neither delayed healing nor increased fungal burdens. The paper does not establish the claimed importance of IL-17- and IL-22-producing TCRβ+ cells specifically. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [25] Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed JA, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42: 356– 366. doi: 10.1016/j.immuni.2015.01.008 25680275 PMC4343045 source

      The Results section, “Compartmentalization of Th cell responses” (page unavailable), reports that Th17 cells protect mice against subsequent cutaneous C. albicans infection. It does not establish a protective role specifically for IL-22-producing TCRβ+ cells or extend that finding to fungal pathogens generally; it distinguishes skin protection by Th17 cells from systemic protection by Th1 cells. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    C. auris enters the dermis and deeper tissues, including hair follicles, unlike other Candida species.

    “Furthermore, C. auris not only colonizes the outer layer of the skin but also enters the dermis and deeper tissues, including hair follicles, a phenomenon that was not observed previously with other Candida species (4, 7).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Results section reports C. auris on the skin surface and deeper in mouse skin tissue, including hair follicles; in the same model, C. albicans did not reside within the skin tissue compartment. The paper does not specifically identify the dermis in these passages, test all other Candida species, or establish deeper-tissue residence in humans; the Discussion describes a human tissue reservoir as a possibility. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [7] Sparber F, De Gregorio C, Steckholzer S, Ferreira FM, Dolowschiak T, Ruchti F, Kirchner FR, Mertens S, Prinz I, Joller N, Buch T, Glatz M, Sallusto F, LeibundGut-Landmann S. 2019. The skin commensal yeast malassezia triggers a type 17 response that coordinates anti-fungal immunity and exacerbates skin inflammation. Cell Host Microbe 25: 389– 403. doi: 10.1016/j.chom.2019.02.002 30870621 source
  • Premisecitation

    U.S. isolates are closely related to those of South America and South Asia.

    “Because U.S. isolates are closely related to those of South America and South Asia, we used the genome sequenced South Asian clade CA 0387 (B8441) to compare with C. albicans (4, 30 – 32).”
    Quote in the paperSubstantial claim4 of 4 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Introduction says C. auris isolates are highly clonal within geographic clades, but does not identify which clades U.S. isolates belong to or compare them genetically with South American and South Asian isolates. Searches for U.S. isolates and their relationship to those clades found no passage establishing the claimed relationship. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [30] Rybak JM, Laura AD, Andrew TN, Katherine SB, Glen EP, P David Rogers R. 2019. Abrogation of Triazole resistance upon deletion of Cdr1 in a clinical isolate of Candida Auris. Antimicrob Agents Chemother 63. doi: 10.1128/aac.00057-19 PMC6437491 30718246 source

      The Results and Discussion identify AR0387 (B8441) as a South Asian-clade isolate, but do not address whether U.S. isolates are closely related to isolates from South America or South Asia. Searches for U.S. isolates and phylogenetic relatedness found no passage establishing that relationship. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [31] Muñoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CA. 2018. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun 9: 5346. doi: 10.1038/s41467-018-07779-6 30559369 PMC6297351 source

      The Introduction identifies South Asian and Venezuelan C. auris clades, and Results > Genome features reports high genomic identity across the four clades. Neither passage identifies U.S. C. auris isolates or shows how they relate to those two regions, so the U.S.-specific claim is unsupported. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [32] Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J, Kemble SK, Pacilli M, Black SR, Landon E, Ridgway J, Palmore TN, Zelzany A, Adams EH, Quinn M, Chaturvedi S, Greenko J, Fernandez R, Southwick K, Furuya EY, Calfee DP, Hamula C, Patel G, Barrett P, MSD, Lafaro P, Berkow EL, Moulton-Meissner H, Noble-Wang J, Fagan RP, Jackson BR, Lockhart SR, Litvintseva AP, Chiller TM. 2016. Investigation of the first seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus - United States, may 2013-August 2016. MMWR Morb Mortal Wkly Rep 65: 1234– 1237. doi: 10. source
  • Premisecitation

    C. auris and C. albicans elicit similar levels of cellular adaptive immune responses in the intestine.

    “However, using an intestinal mouse model of infection, we recently found that C. auris and C. albicans elicit similar levels of cellular adaptive immune responses in the intestine (29).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] Das D, HogenEsch H, Thangamani S. 2023. Intestinal colonization with Candida auris and mucosal immune response in mice treated with Cefoperazone oral antibiotic. Front Immunol 14: 1123200. doi: 10.3389/fimmu.2023.1123200 37114044 PMC10126271 source

      The Results section on adaptive immune response (page not provided) reports increases in intestinal Th17 and Th22 cells in both infected groups, supporting similarity for those cell types. But intestinal Th1 cell numbers were significantly higher in C. auris-infected mice than in C. albicans-infected mice, so the claim overgeneralizes across cellular adaptive responses. The comparison was also specific to cefoperazone-treated mice. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 14
  • May combine two claims. 14
  • The quote only partly states this claim. 2

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

    Premisecitation

    Candida auris was categorized as an urgent threat by the U.S. CDC and classified in the critical priority fungal pathogen group by the WHO.

    “Candida auris was recently categorized as an urgent threat by the U.S. Centers for Disease Control and Prevention (CDC) and classified in the critical priority fungal pathogen group by the World Health Organization (1 – 3).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [1] Ahmad S, Alfouzan W. 2021. Candida auris: epidemiology, diagnosis, pathogenesis, antifungal susceptibility, and infection control measures to combat the spread of infections in healthcare facilities. Microorganisms 9: 807. doi: 10.3390/microorganisms9040807 33920482 PMC8069182 source

      The Conclusions (section 8; page unavailable) call C. auris a serious threat to healthcare, and section 6 describes CDC infection-control guidance. Neither passage states that the CDC categorized it as an urgent threat or that the WHO placed it in a critical-priority group. Searches for both designations found no passage addressing them. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [2] World Health Organization. 2022. WHO fungal priority pathogens list to guide research, development and public health action. World Health Organization, Geneva. Available from: https://www.who.int/publications/i/item/9789240060241

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [3] Kadri SS. 2020. Key takeaways from the U.S. CDC’s 2019 antibiotic resistance threats report for frontline providers. Crit Care Med 48: 939– 945. doi: 10.1097/CCM.0000000000004371 32282351 PMC7176261 source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The flow cytometry gating strategy used identifies the specified immune cell populations.

    “We examined three major APC subsets gated from CD45+ CD11c+ MHCII+ cells: CD11b+ CD207− cells (CD11b+ dendritic cells), CD11b− CD207+ cells (CD103+ dendritic cells), and CD11b+ CD207+ Langerhans cells (LCs) as indicated in Fig. 3A and as described previously (9).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Naik S, Bouladoux N, Linehan JL, Han S-J, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd AL, Deming C, Quinones M, Brenchley JM, Kong HH, Tussiwand R, Murphy KM, Merad M, Segre JA, Belkaid Y. 2015. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520: 104– 108. doi: 10.1038/nature14052 25539086 PMC4667810 source

  • May combine two claims.

    Premisecitation

    Unlike other Candida species, C. auris colonizes human skin, leading to nosocomial transmission and outbreaks of invasive fungal infections.

    “Unlike other Candida species which colonize in the intestine, C. auris colonizes the human skin, which leads to nosocomial transmission and outbreaks of invasive fungal infections (4 – 6).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Introduction says C. auris persists on human skin, unlike Candida species that more typically reside in the gastrointestinal tract. It says skin persistence likely contributes to nosocomial transmission and that colonization is a risk factor for subsequent bloodstream infection; it does not establish that skin colonization necessarily leads to transmission or outbreaks of invasive infection. Page numbers were not provided in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [5] Shastri PS, Shankarnarayan SA, Oberoi J, Rudramurthy SM, Wattal C, Chakrabarti A. 2020. Candida auris candidaemia in an intensive care unit - prospective observational study to evaluate epidemiology, risk factors, and outcome. J Crit Care 57: 42– 48. doi: 10.1016/j.jcrc.2020.01.004 32062286 source
    • cites [6] Proctor DM, Drummond RA, Lionakis MS, Segre JA. 2023. One population, multiple lifestyles: commensalism and pathogenesis in the human mycobiome. Cell Host Microbe 31: 539– 553. doi: 10.1016/j.chom.2023.02.010 37054674 PMC10155287 source

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

    Premisecitation

    T cells such as TCRβ+ IL-17+ T cells are critical for host defense against Candida pathogens, including those in the skin.

    “T cells such as TCRβ+ IL-17+ T cells are critical for host defense against Candida pathogens, including those in the skin (10, 18).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [10] Netea MG, Joosten LAB, van der Meer JWM, Kullberg B-J, van de Veerdonk FL. 2015. Immune defence against Candida fungal infections. Nat Rev Immunol 15: 630– 642. doi: 10.1038/nri3897 26388329 source

      The Effector mechanisms of defence section (pp. 6, 8) says TH17 responses are important against mucosal Candida infection and that IL-17 contributes to host defence. Our copy does not identify TCRβ+ IL-17+ T cells specifically or establish their protective role in skin Candida infections; its skin-related discussion does not make that link. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [18] Kagami S, Rizzo HL, Kurtz SE, Miller LS, Blauvelt A. 2010. IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J Immunol 185: 5453– 5462. doi: 10.4049/jimmunol.1001153 20921529 PMC3076054 source

      The Results (page unavailable) identify CD3+ T cells as the main IL-17A-producing cells in infected mouse skin, and the Abstract reports that IL-17A is required for optimal defense against cutaneous Candida albicans. The paper does not identify those cells as TCRβ+ or establish that this specific T-cell subset is critical; its findings also concern C. albicans rather than Candida pathogens generally. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

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

    Premisecitation

    C. auris elicits less potent innate immune responses compared to C. albicans in the mouse model of systemic infection.

    “Recent evidence indicates that C. auris elicits less potent innate immune responses compared to C. albicans in the mouse model of systemic infection (13).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] Wang Y, Zou Y, Chen X, Li H, Yin Z, Zhang B, Xu Y, Zhang Y, Zhang R, Huang X, Yang W, Xu C, Jiang T, Tang Q, Zhou Z, Ji Y, Liu Y, Hu L, Zhou J, Zhou Y, Zhao J, Liu N, Huang G, Chang H, Fang W, Chen C, Zhou D. 2022. Innate immune responses against the fungal pathogen Candida auris. Nat Commun 13: 3553. doi: 10.1038/s41467-022-31201-x 35729111 PMC9213489 source

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

    Premisecitation

    C. auris colonizes the human skin, which leads to nosocomial transmission and outbreaks of skin infection and candidemia.

    “C. auris colonizes the human skin, which leads to nosocomial transmission and outbreaks of skin infection and candidemia (4, 5).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Introduction says C. auris persists on patients’ skin, likely contributes to nosocomial transmission, and has been involved in outbreaks of skin colonization and/or bloodstream infection. It distinguishes asymptomatic skin colonization from infection, so it does not support the claim of outbreaks of skin infection. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [5] Shastri PS, Shankarnarayan SA, Oberoi J, Rudramurthy SM, Wattal C, Chakrabarti A. 2020. Candida auris candidaemia in an intensive care unit - prospective observational study to evaluate epidemiology, risk factors, and outcome. J Crit Care 57: 42– 48. doi: 10.1016/j.jcrc.2020.01.004 32062286 source

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

    Premisecitation

    A local IL-17A/IL-17F-dependent response mounted by both innate and adaptive lymphoid cell subsets is associated with protection against C. auris skin infection.

    “Using the epicutaneous mouse model of infection, Huang et al. demonstrated that a local IL-17A/IL-17F-dependent response mounted by both innate and adaptive lymphoid cell subsets is associated with protection against C. auris skin infection (4).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

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

    Premisecitation

    C. auris is an emerging multi-drug-resistant fungal pathogen that can cause fatal infections in humans.

    “C. auris is an emerging multi-drug-resistant fungal pathogen that can cause fatal infections in humans (1, 19, 20).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [1] Ahmad S, Alfouzan W. 2021. Candida auris: epidemiology, diagnosis, pathogenesis, antifungal susceptibility, and infection control measures to combat the spread of infections in healthcare facilities. Microorganisms 9: 807. doi: 10.3390/microorganisms9040807 33920482 PMC8069182 source
    • cites [19] Vu CA, Jimenez A, Anjan S, Abbo LM. 2022. Challenges and opportunities in stewardship among solid organ transplant recipients with Candida auris bloodstream infections. Transpl Infect Dis 24: e13919. doi: 10.1111/tid.13919 36254515 source
    • cites [20] Ademe M, Girma F. 2020. Candida auris: from multidrug resistance to pan-resistant strains. Infect Drug Resist 13: 1287– 1294. doi: 10.2147/IDR.S249864 32440165 PMC7211321 source

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

    Premisecitation

    Mice epicutaneously infected with different clades of C. auris had significantly different fungal loads in the skin tissue.

    “Furthermore, mice epicutaneously infected with different clades of C. auris had significantly different fungal loads in the skin tissue (4).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

      The Results section (“Candida auris Persistently Colonizes Skin”; page unavailable) reports that different C. auris clades colonized mouse skin tissue at different levels, with the African clade highest and the South Asian and East Asian clades lowest. The available text does not establish that the differences in skin-tissue fungal loads were statistically significant. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

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

    Premisecitation

    C. albicans morphology, DCs subsets, and LCs elicit different skin immune responses in an epicutaneous and intradermal routes of infection.

    “Previous findings suggest that C. albicans morphology, DCs subsets, and LCs elicit different skin immune responses in an epicutaneous and intradermal routes of infection (25).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [25] Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed JA, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42: 356– 366. doi: 10.1016/j.immuni.2015.01.008 25680275 PMC4343045 source

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

    Premisecitation

    C. auris persisted in mice skin tissue for 4 months even after skin swab was found to be negative for live fungal colonies.

    “C. auris persisted in mice skin tissue for 4 months even after skin swab was found to be negative for live fungal colonies (4).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

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

    Premisecitation

    C. auris persisted longer than C. albicans in kidneys of infected mice.

    “In addition, C. auris persisted longer than C. albicans in kidneys of infected mice (26).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [26] Vila T, Montelongo-Jauregui D, Ahmed H, Puthran T, Sultan AS, Jabra-Rizk MA. 2020. Comparative evaluations of the pathogenesis of Candida auris phenotypes and Candida albicans using clinically relevant murine models of infections. mSphere 5: e00760-20. doi: 10.1128/mSphere.00760-20 32759340 PMC7407074 source

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

    Premisecitation

    Th17 cells are required for cutaneous host defense, while Th1 response is critical against systemic C. albicans infection.

    “Furthermore, previous findings suggest that Th17 cells are required for cutaneous host defense, while Th1 response is critical against systemic C. albicans infection (18, 25).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [18] Kagami S, Rizzo HL, Kurtz SE, Miller LS, Blauvelt A. 2010. IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J Immunol 185: 5453– 5462. doi: 10.4049/jimmunol.1001153 20921529 PMC3076054 source

      The Abstract reports that IL-23 and IL-17A are required for optimal defense against cutaneous C. albicans infection, and says Th1 responses are believed to be critical against C. albicans infection generally. It does not establish that Th17 cells themselves are required in skin or specifically that Th1 responses are critical against systemic infection; the Discussion notes that other cells may produce IL-17A. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [25] Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed JA, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42: 356– 366. doi: 10.1016/j.immuni.2015.01.008 25680275 PMC4343045 source

      The Results section (‘Compartmentalization of Th cell responses’) reports that Th17 cells provided skin protection and Th1 cells provided systemic protection in mice challenged after an earlier infection. That supports the tissue-specific distinction, but the experiments do not establish that either response is required for host defense against all cutaneous or systemic C. albicans infections. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Mice epicutaneously inoculated with C. auris had significantly increased fungal load in the skin swab and underlying skin tissue compartment compared to C. albicans-infected groups.

    “Recent findings indicate that mice epicutaneously inoculated with C. auris had significantly increased fungal load in the skin swab and underlying skin tissue compartment compared to C. albicans-infected groups (4).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [4] Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Belkaid Y, Lionakis MS, Segre JA. 2021. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe 29: 210– 221. doi: 10.1016/j.chom.2020.12.002 33385336 PMC7878403 source

  • May combine two claims.

    Findingown data

    At day 14 post-infection, compared to PBS-injected mice, C. auris-infected mice had significantly increased total numbers of CD4+ T cells, CD8+ T cells, CD4+ IFN-γ+ T cells, CD4+ IL-17A+ T cells, CD4+ IL-17F+ T cells, and CD4+ IL-22+ T cells in skin.

    “Similarly, a significant increase in the total numbers of CD4+ T cells, CD8+ T cells, CD4+ IFN-γ+ T cells, CD4+ IL-17A+ T cells, CD4+ IL-17F+ T cells, and CD4+ IL-22+ T cells was observed in C. auris-infected skin compared to PBS-injected mice (Fig. S5F through J and 5K).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No significant difference in absolute numbers of CD11b+ MHCII+ CD64+ macrophages and CD11b+ Ly6Clow inflammatory monocytes was observed between C. auris- and C. albicans-infected mice at day 3 post-infection.

    “No significant changes were observed in the absolute numbers of CD11b+ MHCII+ CD64+ macrophages and CD11b+ Ly6 Clow inflammatory monocytes between C. auris- and C. albicans-infected groups (Fig. 2C and D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In C. auris-infected mice, IL-17F+ ILCs were significantly increased at day 3 and total ILCs at day 14 compared to PBS-injected mice.

    “Compared to PBS injected mice, C. auris-infected animals had significantly increased numbers of IL-17F+ ILCs (day 3) and total ILCs (day 14) (Fig. S3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At day 14 post-infection, compared to PBS-injected mice, C. auris infection elicited significantly increased total γδ+ T cells and decreased γδ+ IFN-γ+, γδ+ IL-17A+, and γδ+ IL-22+ T cells in skin.

    “At that timepoint, compared to PBS-injected mice, C. auris infection elicited a significantly increased number of total γδ+ T cells and a decreased number of γδ+ IFN-γ+ T cells, γδ+ IL17A+ T cells, and γδ+ IL-22+ T cells (Fig. S4).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In the skin of intradermally infected mice, C. auris infection elicited a significantly increased number of TCRγδ+ IL-17F+ T cells compared to C. albicans infection.

    “C. auris infection elicited a significantly decreased number of total TCRγδ+ T cells and an increased number of TCRγδ+ IL-17F+ T cells (Fig. 5B through E).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    C. auris infection induces significantly decreased numbers of IL-17- and IL-22-producing TCRβ+ T cells.

    “C. auris infection induces significantly decreased numbers of IL-17- and IL-22-producing TCRβ+ T cells”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At day 14 post-infection, compared to PBS-injected mice, C. auris-infected mice had significantly increased numbers of total TCRβ+ T cells, TCRβ+ IFN-γ+ T cells, TCRβ+ IL-17A+ T cells, TCRβ+ IL-17F+ T cells, and TCRβ+ IL-22+ T cells in skin.

    “Compared to PBS-injected mice, C. auris-infected mice had significantly increased numbers of total TCRβ+ T cells, TCRβ+ IFN-γ+ T cells, TCRβ+ IL-17A+ T cells, TCRβ+ IL-17F+ T cells, and TCRβ+ IL-22+ T cells (Fig. S5A through E).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In the skin of intradermally infected mice, C. auris infection elicited a significantly decreased number of total TCRγδ+ T cells compared to C. albicans infection.

    “C. auris infection elicited a significantly decreased number of total TCRγδ+ T cells and an increased number of TCRγδ+ IL-17F+ T cells (Fig. 5B through E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In C. auris-infected mice, skin absolute numbers of CD11b+ DCs, CD103+ DCs, and Langerhans cells were significantly increased at day 3 compared to PBS-injected mice; at day 14, Langerhans cells and CD103+ DCs were increased.

    “At day 3 post-infection, compared to PBS-injected groups, C. auris infection resulted in a significant increase in the absolute numbers of CD11b+ DCs, CD103+DCs, and LCs. At day 14 post-infection, C. auris infection was associated with increased numbers of LCs and CD103+ DCs (Fig. S2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Adaptive immune responses are Candida species specific and may differ in different host mucocutaneous niches such as the gut and skin.

    “These results suggest that adaptive immune responses are Candida species specific and may differ in different host mucocutaneous niches such as the gut and skin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    This study for the first time characterized the major innate immune cells involved in host defense against C. auris skin infection and identified quantitative differences relative to C. albicans skin infection.

    “Our findings for the first time characterized the major innate immune cells involved in host defense against C. auris skin infection and identified quantitative differences relative to C. albicans skin infection.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The innate immune cells involved in the cutaneous host response against C. auris had not been defined to date.
25 of 25

  • The paper relies on this without support.

    The immune factors that contribute to C. auris's unique propensity for skin colonization and long-term persistence are unclear.

    “However, the immune factors that contribute to the unique propensity of C. auris for colonization and long-term persistence in the skin tissue remain unclear.”

  • The paper relies on this without support.

    This study provides the first in vivo comparison of immune cells accumulating in skin of C. auris-infected versus C. albicans-infected mice.

    “Our findings provide the first comparison of the immune cells that accumulate in the skin of C. auris-infected versus C. albicans-infected mice in vivo.”

  • The paper relies on this without support.

    The observed differences between C. auris AR0387 and C. albicans SC5314 are attributable to species differences rather than strain-specific differences.

    “Mice were infected intradermally with C. auris 0387 or C. albicans SC5314 strains.”

  • The paper relies on this without support.

    The intradermal mouse model reflects human C. auris skin colonization and immune responses.

    “These findings help explain the clinical observation of persistent C. auris colonization in skin tissue.”

  • The paper relies on this without support.

    Determinants of colonization resistance and the local host immune response to C. auris in the skin are still poorly defined.

    “However, determinants of colonization resistance and the local host immune response to C. auris in the skin are still poorly defined.”

  • The paper relies on this without support.

    The innate immune cells involved in the cutaneous host response against C. auris had not been defined to date.

    “Although C. auris preferentially colonizes the skin, the innate immune cells involved in the cutaneous host response against C. auris had not been defined to date.”

  • The paper relies on this without support.

    The host factors that contribute to persistent colonization of this emerging pathogen are still not clear.

    “Furthermore, the host factors that contribute to persistent colonization of this emerging pathogen are still not clear.”
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?

  • Fungal colonization was significantly higher in mice skin infected with yeast form of C. auris 0387 strain compared to mice infected with wild-type C. albicans SC5314 which can exist as both yeast and hyphal forms.

    “Recent findings from our lab along with others indicate that fungal colonization was significantly higher in mice skin infected with yeast form of C. auris 0387 strain compared to mice infected with wild-type C. albicans SC5314 which can exist as both yeast and hyphal forms (3, 4).”

    From Yeast and filamentous <i>Candida auris</i> stimulate distinct immune responses in the skin (2024) · cites this paper as [4]

    The Results section (page unavailable) reports significantly higher skin fungal loads in mice infected intradermally with C. auris AR0387 than with C. albicans SC5314 at days 3 and 14. The cited paper identifies both strains, but the passages in our copy do not establish the claim’s additional descriptions of AR0387 as yeast-form or SC5314 as wild-type and capable of both yeast and hyphal forms. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • There are no significant differences in IL-17-mediated immune response among four clades of C. auris.

    “However, previous findings from our laboratory indicated no significant differences in IL-17-mediated immune response among four clades of C. auris [40].”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [40]

    The Results section on differences among C. auris clades reports no significant difference in IL-17-producing T-cell numbers across the four clades. But it also reports significant differences in IL-17A+ and IL-17F+ innate lymphoid cells, so the broader claim that there were no differences in IL-17-mediated immune response overstates the finding. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In an intradermal mouse model, IL-17+ ILCs accumulate in the skin during C. auris infection.

    “In an intradermal mouse model, IL-17+ ILCs accumulated in the skin during C. auris infection [85].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [85]

    The Results section (page not provided) reports increased IL-17F+ ILCs in C. auris-infected skin versus PBS-injected skin at day 3, supporting accumulation of that subset. It does not report a corresponding increase in IL-17A+ ILCs; at day 14, both IL-17A+ and IL-17F+ ILCs accumulated less than in C. albicans-infected skin. The claim omits these subtype, timing, and comparator qualifications. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • C. auris induces a weaker Th17 cell response than C. albicans, which may contribute to its long-term persistence.

    “Notably, C. auris induces a weaker Th17 cell response than C. albicans, which may contribute to its long-term persistence [85].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [85]

    The Results report fewer CD4+ IL-17-producing T cells in C. auris-infected mouse skin than in C. albicans-infected skin, and the Discussion suggests that a weaker immune response may contribute to persistence there. The claim omits that skin-specific mouse-model qualifier; the Discussion also notes similar adaptive cellular responses to the two species in an intestinal model. Page numbers are not provided in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Distinct cytokine requirements exist across mucocutaneous tissues, and IL-17-producing ILCs are key effectors that maintain antifungal barrier immunity in the skin.

    “These findings highlight distinct cytokine requirements across mucocutaneous tissues and underscore IL-17-producing ILCs as key effectors that maintain antifungal barrier immunity in the skin.”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [85]

    The Results section reports fewer IL-17A+ and IL-17F+ ILCs in C. auris-infected mouse skin than in C. albicans-infected skin and describes type 3 ILCs as critical for antifungal defense. The Discussion suggests immune responses may differ between gut and skin, but does not establish distinct cytokine requirements across those tissues. The study measures ILC accumulation rather than demonstrating that IL-17-producing ILCs maintain skin barrier immunity. (LLM, conf=0.84)

    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.

  • Infection dose differs tenfold between Methods and Results

    Major

    The Methods state an inoculum of 1-2 × 10^7 CFU per mouse, while the Results state 1-2 × 10^6 CFU per mouse for the infection experiment.

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Datta, A., Das, D., Nett, J. E., Vyas, J. M., Lionakis, M. S., & Thangamani, S.
Affiliations
  • Purdue University West Lafayette (US)
  • University of Wisconsin–Madison (US)
  • Harvard University (US)
  • National Institutes of Health (US)
ORCID
Venue
Microbiology Spectrum
Publisher
American Society for Microbiology
Published
2023-12-12
Volume
11
Issue
6
Pages
e0221523-e0221523
ISSN
2165-0497 (ISSN-L)
DOI
10.1128/spectrum.02215-23
PMC
PMC10848846
OpenAlex
W4387440635
Semantic Scholar
5397fe2a67eb586d7f743c0dde5cfcc7be87d57f
Cited by
30
References
32
Citations by year
2026: 12 · 2025: 6 · 2024: 11 · 2023: 1
FWCI
5.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Microbiology Spectrum (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Purdue University
  • HHS | NIH | NIAID | Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Health Sciences › Medicine › Epidemiology › Nail Diseases and Treatments
Keywords
Candida auris, Candida albicans, skin colonization, intradermal infection, fungal skin infection, innate immune response, adaptive immune response, neutrophils, inflammatory monocytes, Langerhans cells, ILC3, Th17 cells, fungal load, nosocomial fungal infections, emerging fungal pathogens
MeSH terms
Candida auris, Animals, Antifungal Agents, Candida, Candida albicans, Disease Outbreaks, Immunity, Mice

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.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review