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Cited by 250Antifungal resistance and susceptibilityT-cell and B-cell ImmunologyFungal Infections and Studies

Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation

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Kashem, Sakeen W., Igyártó, Botond Z., Gerami-Nejad, Maryam, Kumamoto, Yosuke, Mohammed, Javed, Jarrett, Elizabeth, Drummond, Rebecca A., Zurawski, Sandra M. +5 more·2015·Immunity
DOI 10.1016/j.immuni.2015.01.008PMC PMC4343045
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Abstract

Candida albicans is a dimorphic fungus responsible for chronic mucocutaneous and systemic infections. Mucocutaneous immunity to C. albicans requires T helper 17 (Th17) cell differentiation that is thought to depend on recognition of filamentous C. albicans. Systemic immunity is considered T cell independent. Using a murine skin infection model, we compared T helper cell responses to yeast and filamentous C. albicans. We found that only yeast induced Th17 cell responses through a mechanism that required Dectin-1-mediated expression of interleukin-6 (IL-6) by Langerhans cells. Filamentous forms induced Th1 without Th17 cell responses due to the absence of Dectin-1 ligation. Notably, Th17 cell responses provided protection against cutaneous infection while Th1 cell responses provided protection against systemic infection. Thus, C. albicans morphology drives distinct T helper cell responses that provide tissue-specific protection. These findings provide insight into compartmentalization of Th cell responses and C. albicans pathogenesis and have critical implications for vaccine strategies.

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  • Fungal morphology plays a critical role in regulating colonization, virulence, and immune response in different host niches including the skin.

    “Previous findings in other Candida species suggest that fungal morphology plays a critical role in regulating the colonization, virulence, and immune response in different host niches including the skin (15).”

    From Yeast and filamentous <i>Candida auris</i> stimulate distinct immune responses in the skin (2024) · cites this paper as [15]

    The Introduction (page unavailable) links the yeast-to-hypha transition to virulence and describes different forms at the skin surface and in deeper tissues. The Introduction and Abstract report morphology-dependent immune responses and tissue-specific protection. The paper does not establish that morphology regulates colonization, so that part of the claim is not supported. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Th17 cells play a critical role in host defense against C. albicans.

    “Th17 cells play a critical role in host defense against C. albicans [30–33,36], whereas Th1 cells protect the host against reinfection from HSV and L. major [34,35].”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [36]

    The Discussion reports that Th17 cells protected against cutaneous C. albicans challenge, supporting their role in host defense. It also states that Th17 expansion did not protect against systemic challenge, so the unqualified claim is broader than this paper's finding. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • IL-17-producing TRM cells play a critical role in host defense against C. albicans during reinfection.

    “Previous findings suggest that IL-17-producing TRM cells play a critical role in host defense against C. albicans during reinfection [30–33,36].”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [36]

    The Results section, “Compartmentalization of Th cell responses” (page unavailable), reports that Th17 cells protected mice against subsequent cutaneous C. albicans challenge. The paper does not establish that those cells were tissue-resident memory (TRM) cells, and its Introduction distinguishes cutaneous protection by Th17 cells from systemic protection by Th1 cells. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • 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.”

    From Differential skin immune responses in mice intradermally infected with <i>Candida auris</i> and <i>Candida albicans</i> (2023) · cites this paper as [25]

    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

  • IL-17-mediated immune responses are critical for protection against C. auris and C. albicans skin infection.

    “These findings suggest that IL-17-mediated immune responses are critical for protection against C. auris and C. albicans skin infection (4, 18, 25).”

    From Differential skin immune responses in mice intradermally infected with <i>Candida auris</i> and <i>Candida albicans</i> (2023) · cites this paper as [25]

    The Results (Compartmentalization of Th cell responses; page not provided) show that Th17 cells protected mice against a subsequent C. albicans skin challenge. The source does not establish the same protection for C. auris, so it supports only the C. albicans portion of the claim. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Authors
Kashem, S. W., Igyártó, B. Z., Gerami-Nejad, M., Kumamoto, Y., Mohammed, J., Jarrett, E., Drummond, R. A., Zurawski, S. M., Zurawski, G., Berman, J., Iwasaki, A., Brown, G. D., & Kaplan, D. H.
Affiliations
  • University of Minnesota (US)
  • Yale University (US)
  • University of Aberdeen (GB)
  • Inserm (FR)
Corresponding author
Kaplan, Daniel H.
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2015-02
Volume
42
Issue
2
Pages
356-366
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2015.01.008
PMC
PMC4343045
OpenAlex
W1965404661
Cited by
250
References
57
Citations by year
2026: 17 · 2025: 17 · 2024: 31 · 2023: 18 · 2022: 18 · 2021: 14 · 2020: 25 · 2019: 23 · 2018: 20 · 2017: 33 · 2016: 18 · 2015: 16
FWCI
22.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
Funders
  • Wellcome Trust (102705, 102705/Z/13/Z)
  • National Institutes of Health (5r01ar056632-05)
  • National Cancer Institute (P30CA077598)
  • National Institute of General Medical Sciences (T32GM008244)
  • National Institute of Allergy and Infectious Diseases (R01AI054359, T32AI007313)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060744, AR060744, AR056632, R01-AR056632)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida albicans, fungal dimorphism, Th17 cell differentiation, Th1 differentiation, dendritic cell subsets, Langerhans cells, Dectin-1, interleukin-6, skin infections, systemic infection, mucocutaneous candidiasis, tissue-specific immunity, antifungal vaccines
MeSH terms
Dectin-1, Animals, Candida albicans, Candidiasis, Chronic Mucocutaneous, Cell Differentiation, Dendritic Cells, Langerhans Cells, Lymphocyte Activation, Mice, Inbred C57BL, Repressor Proteins, Skin, Interleukin-6, Mice, Knockout, Th1 Cells, Lectins, C-Type, Basic-Leucine Zipper Transcription Factors, Mice, Th17 Cells

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