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Cited by 125T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisDermatology and Skin Diseases

Staged development of long-lived T-cell receptor αβ TH17 resident memory T-cell population to Candida albicans after skin infection

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Park, Chang Ook, Fu, Xiujun, Jiang, Xiaodong, Pan, Youdong, Teague, Jessica E., Collins, Nicholas, Tian, Tian, O'Malley, John T. +10 more·2018·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2017.09.042PMC PMC5943196
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Abstract

Background Candida albicans is a dimorphic fungus to which human subjects are exposed early in life, and by adulthood, it is part of the mycobiome of skin and other tissues. Neonatal skin lacks resident memory T (T RM) cells, but in adults the C albicans skin test is a surrogate for immunocompetence. Young adult mice raised under specific pathogen-free conditions are naive to C albicans and have been shown recently to have an immune system resembling that of neonatal human subjects. Objective We studied the evolution of the adaptive cutaneous immune response to Candida species. Methods We examined both human skin T cells and the de novo and memory immune responses in a mouse model of C albicans skin infection. Results In mice the initial IL-17-producing cells after C albicans infection were dermal γδ T cells, but by day 7, αβ T H 17 effector T cells were predominant. By day 30, the majority of C albicans-reactive IL-17-producing T cells were CD4 T RM cells. Intravital microscopy showed that CD4 effector T cells were recruited to the site of primary infection and were highly motile 10 days after infection. Between 30 and 90 days after infection, these CD4 T cells became increasingly sessile, acquired expression of CD69 and CD103, and localized to the papillary dermis. These established T RM cells produced IL-17 on challenge, whereas motile migratory memory T cells did not. T RM cells rapidly clear an infectious challenge with C albicans more effectively than recirculating T cells, although both populations participate. We found that in normal human skin IL-17-producing CD4+ T RM cells that responded to C albicans in an MHC class II-restricted fashion could be identified readily. Conclusions These studies demonstrate that C albicans infection of skin preferentially generates CD4+ IL-17-producing T RM cells, which mediate durable protective immunity.

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  • Effector T cells play a critical role in the host's defense during reinfection with C. albicans, Staphylococcus aureus, Leishmania major, and HSV.

    “Effector T cells play a critical role in the host’s defense during reinfection with C. albicans, Staphylococcus aureus, Leishmania major, and HSV [28,30–35].”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [33]

    The Results section (‘Skin CD4 T cells present after cutaneous C. albicans infection are pathogen-specific’; page unavailable) shows that skin-resident memory T cells protected mice against C. albicans reinfection. The Discussion also mentions protective T-cell immunity after skin viral infection, but the paper does not establish the claimed reinfection defense against Staphylococcus aureus or Leishmania major; it lists a Leishmania study only in its references. The demonstrated protective cells are resident memory T cells, rather than effector T cells at reinfection. (LLM, conf=0.88)

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  • 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 [33]

  • 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 [33]

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Authors
Park, C. O., Fu, X., Jiang, X., Pan, Y., Teague, J. E., Collins, N., Tian, T., O'Malley, J. T., Emerson, R. O., Kim, J. H., Jung, Y., Watanabe, R., Fuhlbrigge, R. C., Carbone, F. R., Gebhardt, T., Clark, R. A., Lin, C. P., & Kupper, T. S.
Affiliations
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
  • The University of Melbourne (AU)
  • Adaptive Biotechnologies (United States) (US)
  • Yonsei University (KR)
Corresponding author
Kupper, Thomas S.
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2018-08
Volume
142
Issue
2
Pages
647-662
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2017.09.042
PMC
PMC5943196
OpenAlex
W2767952161
Cited by
125
References
5
Citations by year
2026: 7 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 12 · 2021: 24 · 2020: 23 · 2019: 11 · 2018: 13 · 2017: 1
FWCI
5.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders
  • National Cancer Institute (R01CA203721)
  • National Institute of Allergy and Infectious Diseases (R01AI041707, R01AI127654, R01AI097128)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR063962, R01AR065807, P30AR069625)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords
Candida albicans, tissue-resident memory T cells, Th17 cells, IL-17, skin infections, skin immunity, CD4+ T cells, γδ T cells, CD69, CD103, T cell homing, MHC class II restriction, fungal infection, immunocompetence, intravital microscopy
MeSH terms
Adult, Animals, Candida albicans, Candidiasis, Cell Differentiation, Cell Movement, Cells, Cultured, Disease Models, Animal, Humans, Immunocompetence, Immunologic Memory, Infant, Newborn, Mice, Inbred C57BL, Skin, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, alpha-beta, Interleukin-17, Mice, Adaptive Immunity, Th17 Cells

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