Cutaneous innate lymphoid populations drive IL-17A-mediated immunity in Nannizzia gypsea dermatophytosis
Open accessAbstract
Fungal skin infections significantly contribute to the global human disease burden, yet our understanding of cutaneous immunity against dermatophytes remains limited. Previously, we developed a model of epicutaneous infection with Microsporum canis in C57BL/6 mice, which highlighted the critical role of IL-17RA signaling in antidermatophyte defenses. In this study, we expanded our investigation to the human pathogen Nannizzia gypsea and demonstrated that skin γδTCR int and CD8/CD4 double-negative βTCR+ T cells are the principal producers of IL-17A during dermatophytosis. These IL-17A+ T cells exhibited an activated/memory phenotype, including a subset of proliferating tissue-resident cells. Notably, restriction of lymphocyte trafficking after fingolimod administration in infected mice did not lead to increased susceptibility, indicating that local antifungal defenses are independent of T-cell priming in lymph nodes. In addition, Rag1-/- mice lacking T and B lymphocytes effectively controlled infection and exhibited increased IL-17A production by innate lymphoid cells. Furthermore, Rag2-/-Il2rg-/- mice, devoid of T, B, and innate lymphoid cells, were highly susceptible to dermatophytosis compared with Rag2-/-or wild-type mice, demonstrating that innate lymphoid cells are sufficient to antifungal defenses in T-cell-deficient mice. In conclusion, our study underscores the coordinated interplay between skin γδT, αβT, and innate lymphoid cell subsets in controlling primary N gypsea dermatophytosis.
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ILCs contribute to effective host defense against mucocutaneous fungal challenge.
“ILCs contribute to effective host defense against mucocutaneous fungal challenge [92,93].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [93]
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Cites
Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision
Bongomin, F., Gago, S., Oladele, R., & Denning, D. (2017) · Journal of Fungi · doi:10.3390/jof3040057 · Cited by 2,953 · see citing works
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., Allende, M. L., Proia, R. L., & Cyster, J. G. (2004) · Nature · doi:10.1038/nature02284 · Cited by 2,581 · see citing works
Innate Lymphoid Cells: 10 Years On
Vivier, É., Artis, D., Colonna, M., Diefenbach, A., Santo, J. P. D., Eberl, G., Koyasu, S., Locksley, R. M., McKenzie, A. N. J., Mebius, R. E., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.017 · Cited by 2,136 · see citing works
Homeostatic Immunity and the Microbiota
Belkaid, Y., & Harrison, O. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.008 · Cited by 1,261 · see citing works
Conti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J., Ho, A. W., Hai, J. H., Yu, J. J., Jung, J. W., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081463 · Cited by 1,024 · see citing works
IL-17 and IL-17-producing cells in protection versus pathology
Mills, K. H. G. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00746-9 · Cited by 1,023 · see citing works
Pivotal Role of Dermal IL-17-Producing γδ T Cells in Skin Inflammation
Cai, Y., Shen, X., Ding, C., Qi, C., Li, K., Li, X., Jala, V. R., Zhang, H., Wang, T., Zheng, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.001 · Cited by 1,021 · see citing works
Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity
Jiang, X., Clark, R. A., Liu, L., Wagers, A. J., Fuhlbrigge, R. C., & Kupper, T. S. (2012) · Nature · doi:10.1038/nature10851 · Cited by 883 · see citing works
Commensal–dendritic-cell interaction specifies a unique protective skin immune signature
Naik, S., Bouladoux, N., Linehan, J. L., Han, S.-J., Harrison, O. J., Wilhelm, C., Conlan, S., Himmelfarb, S., Byrd, A. L., Deming, C., et al. (2015) · Nature · doi:10.1038/nature14052 · Cited by 820 · see citing works
Location, location, location: Tissue resident memory T cells in mice and humans
Szabo, P. A., Miron, M., & Farber, D. L. (2019) · Science Immunology · doi:10.1126/sciimmunol.aas9673 · Cited by 651 · see citing works
MAIT cells are imprinted by the microbiota in early life and promote tissue repair
Constantinides, M. G., Link, V. M., Tamoutounour, S., Wong, A. C., Perez-Chaparro, P. J., Han, S.-J., Chen, Y. E., Li, K., Farhat, S., Weckel, A., et al. (2019) · Science · doi:10.1126/science.aax6624 · Cited by 567 · see citing works
IL-17 receptor–based signaling and implications for disease
Li, X., Bechara, R., Zhao, J., McGeachy, M. J., & Gaffen, S. L. (2019) · Nature Immunology · doi:10.1038/s41590-019-0514-y · Cited by 554 · see citing works
Igyártó, B. Z., Haley, K. M., Ortner, D., Bobr, A., Gerami‐Nejad, M., Edelson, B. T., Zurawski, S., MALISSEN, B., Zurawski, G., Berman, J. G., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.06.005 · Cited by 429 · see citing works
Deep Dermatophytosis and Inherited CARD9 Deficiency
Lanternier, F., Pathan, S., Vincent, Q. B., Liu, L., Cypowyj, S., Prando, C., Migaud, M., Taibi, L., Ammar-Khodja, A., Stambouli, O. B., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1208487 · Cited by 394 · see citing works
Gladiator, A., Wangler, N., Trautwein-Weidner, K., & LeibundGut-Landmann, S. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202924 · Cited by 382 · see citing works
Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response
Faraco, G., Brea, D., Garcia-Bonilla, L., Wang, G., Racchumi, G., Chang, H., Buendia, I., Santisteban, M. M., Segarra, S. G., Koizumi, K., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0059-z · Cited by 343 · see citing works
CD3(+)CD4(-)CD8(-) (Double-negative) T cells in inflammation, immune disorders and cancer
Wu, Z., Zheng, Y., Sheng, J., Han, Y., Yang, Y., Pan, H., & Yao, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.816005 · Cited by 265 · see citing works
Sparber, F., De Gregorio, C., Steckholzer, S., Ferreira, F. M., Dolowschiak, T., Ruchti, F., Kirchner, F. R., Mertens, S., Prinz, I., Joller, N., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.02.002 · Cited by 255 · see citing works
Self-citationCandida albicans morphology and dendritic cell subsets determine T helper cell differentiation
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., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.008 · Cited by 250 · see citing works
T cells and the skin: from protective immunity to inflammatory skin disorders
Ho, A. W., & Kupper, T. S. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0162-3 · Cited by 241 · see citing works
Skin-resident innate lymphoid cells converge on a pathogenic effector state
Bielecki, P., Riesenfeld, S. J., Hütter, J.-C., Triglia, E. T., Kowalczyk, M. S., Ricardo-González, R. R., Lian, M., Vesely, M. C. A., Kroehling, L., Xu, H. Y., et al. (2021) · Nature · doi:10.1038/s41586-021-03188-w · Cited by 218 · see citing works
Aberrant type 1 immunity drives susceptibility to mucosal fungal infections.
Break, T. J., Oikonomou, V., Dutzan, N., Desai, J. V., Swidergall, M., Freiwald, T., Chauss, D., Harrison, O. J., Alejo, J., Williams, D. W., et al. (2021) · Science · doi:10.1126/science.aay5731 · Cited by 175 · see citing works
Self-citationRichmond, J. M., Strassner, J. P., Rashighi, M., Agarwal, P., Garg, M., Essien, K. I., Pell, L., & Harris, J. E. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.10.032 · Cited by 152 · see citing works
Skin Immunity to Candida albicans
Kashem, S. W., & Kaplan, D. H. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.04.007 · Cited by 150 · see citing works
Huang, X., Hurabielle, C., Drummond, R. A., Bouladoux, N., Desai, J. V., Sim, C. K., Belkaid, Y., Lionakis, M. S., & Segre, J. A. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2020.12.002 · Cited by 144 · see citing works
Self-citationGenetic models reveal origin, persistence and non-redundant functions of IL-17–producing γδ T cells
Sandrock, I., Reinhardt, A., Ravens, S., Binz, C., Wilharm, A., Barros‐Martins, J., Oberdörfer, L., Tan, L., Lienenklaus, S., Zhang, B., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20181439 · Cited by 141 · see citing works
Self-citationTan, L., Sandrock, I., Odak, I., Aizenbud, Y., Wilharm, A., Barros‐Martins, J., Tabib, Y., Borchers, A., Amado, T., Gangoda, L., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.064 · Cited by 126 · see citing works
Self-citationPark, 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., et al. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.09.042 · Cited by 125 · see citing works
Balogh, K. N., Templeton, D. J., & Cross, J. V. (2018) · PLoS ONE · doi:10.1371/journal.pone.0197702 · Cited by 103 · see citing works
Early-life imprinting of unconventional T cells and tissue homeostasis
Constantinides, M. G., & Belkaid, Y. (2021) · Science · doi:10.1126/science.abf0095 · Cited by 100 · see citing works
Immunity to commensal skin fungi promotes psoriasiform skin inflammation
Hurabielle, C., Link, V. M., Bouladoux, N., Han, S.-J., Merrill, E. D., Lightfoot, Y. L., Seto, N., Bleck, C. K. E., Smelkinson, M., Harrison, O. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003022117 · Cited by 97 · see citing works
Self-citationDouble‐negative T cells: Setting the stage for disease control or progression
Velikkakam, T., Gollob, K. J., & Dutra, W. O. (2021) · Immunology · doi:10.1111/imm.13441 · Cited by 94 · see citing works
Dermatophyte infection: from fungal pathogenicity to host immune responses
Deng, R., Wang, X., & Li, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1285887 · Cited by 86 · see citing works
Skin Immunity to Dermatophytes: From Experimental Infection Models to Human Disease
Burstein, V. L., Beccacece, I., Guasconi, L., Mena, C. J., Cervi, L., & Chiapello, L. S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.605644 · Cited by 78 · see citing works
Self-citationTCR + CD3 + CD4 − CD8 − effector T cells in psoriasis
Brandt, D., Sergon, M., Abraham, S., Mäbert, K., & Hedrich, C. M. (2017) · Clinical Immunology · doi:10.1016/j.clim.2017.06.002 · Cited by 59 · see citing works
Jiang, X., Park, C. O., Geddes-Sweeney, J., Yoo, M. J., Gaide, O., & Kupper, T. S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169397 · Cited by 53 · see citing works
Sparber, F., Dolowschiak, T., Mertens, S., Lauener, L., Clausen, B., Joller, N., Stoitzner, P., Tussiwand, R., & Leibundgut-Landmann, S. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007069 · Cited by 52 · see citing works
Burstein, V. L., Guasconi, L., Beccacece, I., Theumer, M. G., Mena, C. J., Prinz, I., Cervi, L., Herrero, M., Masih, D. T., & Chiapello, L. S. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.02.042 · Cited by 49 · see citing works
Self-citationTh1 and Th17 Immune Responses Act Complementarily to Optimally Control Superficial Dermatophytosis
Heinen, M.-P., Cambier, L., Antoine, N., Gabriel, A., Gillet, L., Bureau, F., & Mignon, B. R. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.07.040 · Cited by 48 · see citing works
Nielsen, J., Kofod‐Olsen, E., Spaun, E., Larsen, C. S., Christiansen, M., & Mogensen, T. H. (2015) · BMJ Case Reports · doi:10.1136/bcr-2015-211372 · Cited by 38 · see citing works
Ueyama, A., Imura, C., Fusamae, Y., Tsujii, K., Furue, Y., Aoki, M., Suzuki, M., Okuda, T., Oshima, I., Yasui, K., et al. (2016) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2016.10.007 · Cited by 29 · see citing works
Iwasawa, M., Miyachi, H., Wakabayashi, S., Sugihira, T., Aoyama, R., Nakagawa, S., Katayama, Y., Yoneyama, M., Hara, H., Iwakura, Y., et al. (2022) · International Immunology · doi:10.1093/intimm/dxac019 · Cited by 18 · see citing works
Innate Lymphoid Cells in Skin Homeostasis and Malignancy
Wagner, M., & Koyasu, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.758522 · Cited by 17 · see citing works
Immunological response and clinical profile in patients with recurrent dermatophytosis
Jha, K., Shaw, D., Karim, A., Narang, T. K., Saikia, B., Rudramurthy, S. M., Saikia, U. N., & Dogra, S. (2021) · Mycoses · doi:10.1111/myc.13322 · Cited by 17 · see citing works
Helper T cell immunity in humans with inherited CD4 deficiency
Guérin, A., Moncada‐Vélez, M., Jackson, K., Ogishi, M., Rosain, J., Mancini, M., Langlais, D., Nunez, A. C., Webster, S., Goyette, J., et al. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20231044 · Cited by 15 · see citing works
Sawada, Y., Nakamura, M., Kabashima‐Kubo, R., Shimauchi, T., Kobayashi, M., & TOKURA, Y. (2013) · Clinical Immunology · doi:10.1016/j.clim.2013.03.013 · Cited by 14 · see citing works
Tissue-resident memory T cells in antifungal immunity.
LeibundGut-Landmann, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.693055 · Cited by 10 · see citing works
Ruchti, F., Tuor, M., Mathew, L., McCarthy, N. E., & LeibundGut‐Landmann, S. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1011668 · Cited by 9 · see citing works
Flagged first, then by citations
1 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
- Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. Journal of Experimental Medicine. 2009b; 206(2): 299– 311 19204111 PMC2646568
- Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host & Microbe. 2021b; 29(2): 210– 221. e6 33385336 PMC7878403
- Hurabielle C, Link VM, Bouladoux N, Han S-J, Merrill ED, Lightfoot YL, Immunity to commensal skin fungi promotes psoriasiform skin inflammation. Proc. Natl. Acad. Sci. U.S.A 2020b; 117(28): 16465– 74 32601220 PMC7368261
- Iwasawa MT, Miyachi H, Wakabayashi S, Sugihira T, Aoyama R, Nakagawa S, Epidermal clearance of Candida albicans is mediated by IL-17 but independent of fungal innate immune receptors. International Immunology. 2022b; 34(8): 409– 20 35641096 PMC9317997
- Iwasawa MT, Miyachi H, Wakabayashi S, Sugihira T, Aoyama R, Nakagawa S, Epidermal clearance of Candida albicans is mediated by IL-17 but independent of fungal innate immune receptors. International Immunology. 2022c; 34(8): 409– 20 35641096 PMC9317997
- Kashem SW, Kaplan DH. Skin Immunity to Candida albicans. Trends Immunol 2016b; 37(7): 440– 50 27178391 PMC4931795
- Park CO, Fu X, Jiang X, Pan Y, Teague JE, Collins N, Staged development of long-lived T-cell receptor αβ T H 17 resident memory T-cell population to Candida albicans after skin infection. Journal of Allergy and Clinical Immunology. 2018b; 142(2): 647– 62 29128674 PMC5943196
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Candida auris : host interactions, antifungal drug resistance, and diagnostics
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Self-citationHost–Candida auris interactions in the skin
Thangamani, S., Balakumar, A., Datta, A., Bryak, G., & Lionakis, M. S. (2026) · PLOS Pathogens · doi:10.1371/journal.ppat.1014075 · Cited by 3 · see citing works
Self-citationThe natural history and evolution of dermatophytosis: Host immunity in acute and chronic infection
Gupta, A. K., Wang, T., Chowdhary, A., Saunte, D. M. L., Hay, R. J., & Piguet, V. (2026) · PLoS Pathogens · doi:10.1371/journal.ppat.1014264 · Cited by 1 · see citing works
- Authors
- Beccacece, I., Burstein, V. L., Almeida, M. A., Gareca, J. C., Guasconi, L., Mena, C. J., Mary, V. S., Theumer, M. G., Cervi, L., Prinz, I., Gruppi, A., Lionakis, M. S., & Chiapello, L. S.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- University Medical Center Hamburg-Eppendorf (DE)
- National Institutes of Health (US)
- Corresponding author
- Chiapello, Laura Silvina
- ORCID
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2025-07
- Volume
- 145
- Issue
- 7
- Pages
- 1706-1716.e4
- ISSN
- 0022-202X (ISSN-L)
- PMC
- PMC12183320
- OpenAlex
- W4405694609
- Cited by
- 3
- References
- 49
- Citations by year
- 2026: 2 · 2025: 1
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Conicet (publishedVersion, cc-by-nc-sa)
- Funders
- Agencia Nacional De Promoción Científica Y Tecnológica
- CONICET
- NIAID (ZIA AI001175)
- Fulbright US Scholar Program
- Universidad Nacional de Córdoba
- Division of Intramural Research
- Secretaría de Ciencia y Técnica, Universidad Nacional de Río Cuarto
- National Institutes of Health
- Universidad Nacional de Cordoba Secretaria de Ciencia y Tecnologia
- International Union of Biochemistry and Molecular Biology
- Fondo para la Investigación Científica y Tecnológica (PICT 2018-01349, PICT 2021-00483)
- Topics
- Health Sciences › Medicine › Epidemiology › Nail Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- Microsporum gypseum, dermatophytosis, IL-17A, innate lymphoid cells, γδ T cells, double-negative T cells, antifungal immunity, Rag1-deficient mice, Rag2-deficient mice, fingolimod, lymphocyte migration, tissue-resident memory T cells, fungal skin infection
- MeSH terms
- Animals, Arthrodermataceae, Disease Models, Animal, Humans, Immunity, Innate, Mice, Inbred C57BL, Skin, Tinea, Receptors, Antigen, T-Cell, gamma-delta, Mice, Knockout, Interleukin-17, Mice
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