Leonardi, I. et al. Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity. Cell 185, 831–846.e14 (2022).
Shao, T. Y. et al. Commensal Candida albicans positively calibrates systemic Th17 immunological responses. Cell Host Microbe 25, 404–417.e6 (2019).
Tso, G. H. W. et al. Experimental evolution of a fungal pathogen into a gut symbiont. Science 362, 589–595 (2018).
Li, X. V., Leonardi, I. & Iliev, I. D. Gut mycobiota in immunity and inflammatory disease. Immunity 50, 1365–1379 (2019).
Zeng, S. et al. Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease. Cell Host Microbe 31, 389–404.e7 (2023).
Bacher, P. et al. Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176, 1340–1355.e15 (2019).
Lu, S. Y. Oral candidosis: pathophysiology and best practice for diagnosis, classification, and successful management. J. Fungi 7, 555 (2021).
Denning, D. W., Kneale, M., Sobel, J. D. & Rautemaa-Richardson, R. Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect. Dis. 18, e339–e347 (2018).
Denning, D. W. Global incidence and mortality of severe fungal disease. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(23)00692-8 (2024).
Fróis-Martins, R., Lagler, J. & LeibundGut-Landmann, S. Candida albicans virulence traits in commensalism and disease. Curr. Clin. Microbiol. Rep. https://doi.org/10.1007/s40588-024-00235-8 (2024).
d’Enfert, C. et al. The impact of the fungus–host–microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol. Rev. 45, fuaa060 (2021).
Kirchner, F. R. & LeibundGut-Landmann, S. Tissue-resident memory Th17 cells maintain stable fungal commensalism in the oral mucosa. Mucosal Immunol. 14, 455–467 (2021).
Park, C. O. et al. Staged development of long-lived T-cell receptor alphabeta T(H)17 resident memory T-cell population to Candida albicans after skin infection. J. Allergy Clin. Immunol. 142, 647–662 (2018).
Kirchner, F. R. et al. Persistence of Candida albicans in the oral mucosa induces a curbed inflammatory host response that is independent of immunosuppression. Front. Immunol. 10, 330 (2019).
Schonherr, F. A. et al. The intraspecies diversity of C. albicans triggers qualitatively and temporally distinct host responses that determine the balance between commensalism and pathogenicity. Mucosal Immunol. 10, 1335–1350 (2017).
Lionakis, M. S., Drummond, R. A. & Hohl, T. M. Immune responses to human fungal pathogens and therapeutic prospects. Nat. Rev. Immunol. 23, 433–452 (2023).
Conti, H. R. et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J. Exp. Med. 206, 299–311 (2009).
Anderson, F. M. et al. Candida albicans selection for human commensalism results in substantial within-host diversity without decreasing fitness for invasive disease. PLoS Biol. 21, e3001822 (2023).
Puel, A. et al. Inborn errors of mucocutaneous immunity to Candida albicans in humans: a role for IL-17 cytokines? Curr. Opin. Immunol. 22, 467–474 (2010).
Bougnoux, M. E. et al. Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med. 34, 292–299 (2008).
Zelante, T. et al. Sensing of mammalian IL-17A regulates fungal adaptation and virulence. Nat. Commun. 3, 683 (2012).
Glocker, E. O. et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 361, 1727–1735 (2009).
Luo, G. et al. A human commensal-pathogenic fungus suppresses host immunity via targeting TBK1. Cell Host Microbe 32, 1536–1551.e6 (2024).
Majer, O. et al. Type I interferons promote fatal immunopathology by regulating inflammatory monocytes and neutrophils during Candida infections. PLoS Pathog. 8, e1002811 (2012).
Pekmezovic, M. et al. Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells. Nat. Microbiol. 6, 643–657 (2021).
Li, T., Niu, X., Zhang, X., Wang, S. & Liu, Z. Recombinant human IFNα-2b response promotes vaginal epithelial cells defense against Candida albicans. Front. Microbiol. 8, 697 (2017).
Break, T. J. et al. Aberrant type 1 immunity drives susceptibility to mucosal fungal infections. Science 371, eaay5731 (2021).
Piehler, D. et al. The IL-33 receptor (ST2) regulates early IL-13 production in fungus-induced allergic airway inflammation. Mucosal Immunol. 9, 937–949 (2016).
Aggor, F. E. Y. et al. Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis. Sci. Immunol. 5, eaba0570 (2020).
Millet, N. et al. Non-canonical IL-22 receptor signaling remodels the mucosal barrier during fungal immunosurveillance. Preprint at bioRxiv https://doi.org/10.1101/2024.09.08.611873 (2024).
Lee, J. S. et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity 43, 727–738 (2015).
Kumar, P. et al. Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation. Immunity 44, 659–671 (2016).
Chiricozzi, A. et al. Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J. Invest. Dermatol. 131, 677–687 (2011).
Conti, H. R. et al. IL-17 receptor signaling in oral epithelial cells is critical for protection against oropharyngeal candidiasis. Cell Host Microbe 20, 606–617 (2016).
Krishnakumari, V., Rangaraj, N. & Nagaraj, R. Antifungal activities of human beta-defensins HBD-1 to HBD-3 and their C-terminal analogs Phd1 to Phd3. Antimicrob. Agents Chemother. 53, 256–260 (2009).
Jukic, A., Bakiri, L., Wagner, E. F., Tilg, H. & Adolph, T. E. Calprotectin: from biomarker to biological function. Gut 70, 1978–1988 (2021).
Christmann, C. et al. Interleukin 17 promotes expression of alarmins S100A8 and S100A9 during the inflammatory response of keratinocytes. Front. Immunol. 11, 599947 (2020).
Trautwein-Weidner, K., Gladiator, A., Nur, S., Diethelm, P. & LeibundGut-Landmann, S. IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils. Mucosal Immunol. 8, 221–231 (2015).
Zygiel, E. M. & Nolan, E. M. Transition metal sequestration by the host-defense protein calprotectin. Annu. Rev. Biochem. 87, 621–643 (2018).
Citiulo, F. et al. Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLoS Pathog. 8, e1002777 (2012).
Loboda, D. & Rowinska-Zyrek, M. Zinc binding sites in Pra1, a zincophore from Candida albicans. Dalton Trans. 46, 13695–13703 (2017).
Alamir, O. F., Oladele, R. O. & Ibe, C. Nutritional immunity: targeting fungal zinc homeostasis. Heliyon 7, e07805 (2021).
Roselletti, E. et al. Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein. Sci. Transl. Med. 15, eadi3363 (2023).
Besold, A. N. et al. Role of calprotectin in withholding zinc and copper from Candida albicans. Infect. Immun. 86, e00779-17 (2018).
Clark, H. L. et al. Zinc and manganese chelation by neutrophil S100A8/A9 (calprotectin) limits extracellular Aspergillus fumigatus hyphal growth and corneal infection. J. Immunol. 196, 336–344 (2016).
Cho, Y. E. et al. Cellular Zn depletion by metal ion chelators (TPEN, DTPA and chelex resin) and its application to osteoblastic MC3T3-E1 cells. Nutr. Res. Pract. 1, 29–35 (2007).
Sitterlé, E. La candidose cutanéo-muqueuse chronique: un modèle d’étude de l’adaptation génomique chez Candida albicans. Doctoral thesis, Doctoral school BioScience Paris Cité (2018).
Puel, A. et al. Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr. Opin. Allergy Clin. Immunol. 12, 616–622 (2012).
Murdoch, C. C. & Skaar, E. P. Nutritional immunity: the battle for nutrient metals at the host–pathogen interface. Nat. Rev. Microbiol. 20, 657–670 (2022).
Naik, S. et al. Compartmentalized control of skin immunity by resident commensals. Science 337, 1115–1119 (2012).
Naik, S. et al. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520, 104–108 (2015).
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Solis, N. V., Wakade, R. S., Filler, S. G. & Krysan, D. J. Candida albicans oropharyngeal infection is an exception to iron-based nutritional immunity. mBio 14, e0009523 (2023).
Wolk, K. et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur. J. Immunol. 36, 1309–1323 (2006).
Nograles, K. E. et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br. J. Dermatol. 159, 1092–1102 (2008).
Dalessandri, T., Crawford, G., Hayes, M., Castro Seoane, R. & Strid, J. IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin. Nat. Commun. 7, 12080 (2016).
Dixon, B. R., Radin, J. N., Piazuelo, M. B., Contreras, D. C. & Algood, H. M. IL-17a and IL-22 induce expression of antimicrobials in gastrointestinal epithelial cells and may contribute to epithelial cell defense against Helicobacter pylori. PLoS ONE 11, e0148514 (2016).
Pettas, E., Savva, V., Theofilou, V. I., Georgaki, M. & Nikitakis, N. G. Oral Candida infection in psoriatic patients treated with IL17A inhibitors: report of 3 cases and a comprehensive review of the literature. Diagnostics 12, 3 (2021).
Huang, M. Y., Woolford, C. A., May, G., McManus, C. J. & Mitchell, A. P. Circuit diversification in a biofilm regulatory network. PLoS Pathog. 15, e1007787 (2019).
Bartell, J. A. et al. Evolutionary highways to persistent bacterial infection. Nat. Commun. 10, 629 (2019).
Wartenberg, A. et al. Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant. PLoS Genet. 10, e1004824 (2014).
Pradhan, A. et al. Anticipatory stress responses and immune evasion in fungal pathogens. Trends Microbiol. 29, 416–427 (2021).
Ene, I. V. et al. Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen. Proc. Natl Acad. Sci. USA 115, E8688–E8697 (2018).
Zenewicz, L. A. IL-22 binding protein (IL-22BP) in the regulation of IL-22 biology. Front. Immunol. 12, 766586 (2021).
Donnelly, R. P. et al. Interleukin-26: an IL-10-related cytokine produced by Th17 cells. Cytokine Growth Factor Rev. 21, 393–401 (2010).
Ropars, J. et al. Gene flow contributes to diversification of the major fungal pathogen Candida albicans. Nat. Commun. 9, 2253 (2018).
Kozlov, A. M., Darriba, D., Flouri, T., Morel, B. & Stamatakis, A. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 35, 4453–4455 (2019).
Letunic, I. & Bork, P. Interactive Tree of Life (iTOL) v6: recent updates to the phylogenetic tree display and annotation tool. Nucleic Acids Res. 52, W78–W82 (2024).
Rupniak, H. T. et al. Characteristics of four new human cell lines derived from squamous cell carcinomas of the head and neck. J. Natl Cancer Inst. 75, 621–635 (1985).
Parikh, N., Nagarajan, P., Sei-ichi, M., Sinha, S. & Garrett-Sinha, L. A. Isolation and characterization of an immortalized oral keratinocyte cell line of mouse origin. Arch. Oral. Biol. 53, 1091–1100 (2008).
Wachtler, B., Wilson, D., Haedicke, K., Dalle, F. & Hube, B. From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells. PLoS ONE 6, e17046 (2011).
Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671–675 (2012).
Noben-Trauth, N. et al. An interleukin 4 (IL-4)-independent pathway for CD4+ T cell IL-4 production is revealed in IL-4 receptor-deficient mice. Proc. Natl Acad. Sci. USA 94, 10838–10843 (1997).
Muller, U. et al. Functional role of type I and type II interferons in antiviral defense. Science 264, 1918–1921 (1994).
Huang, S. et al. Immune response in mice that lack the interferon-gamma receptor. Science 259, 1742–1745 (1993).
Haas, J. D. et al. Development of interleukin-17-producing γδ T cells is restricted to a functional embryonic wave. Immunity 37, 48–59 (2012).
Kreymborg, K. et al. IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J. Immunol. 179, 8098–8104 (2007).
Sparber, F. et al. 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.e6 (2019).
Blache, D., Martin, G. B. & Maloney, S. K. Towards ethically improved animal experimentation in the study of animal reproduction. Reprod. Domest. Anim. 43, 8–14 (2008).
Solis, N. V. & Filler, S. G. Mouse model of oropharyngeal candidiasis. Nat. Protoc. 7, 637–642 (2012).
Cossarizza, A. et al. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur. J. Immunol. 49, 1457–1973 (2019).
Hatakeyama, M. et al. SUSHI: an exquisite recipe for fully documented, reproducible and reusable NGS data analysis. BMC Bioinformatics 17, 228 (2016).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Frankish, A. et al. Gencode 2021. Nucleic Acids Res. 49, D916–D923 (2021).
Liao, Y., Smyth, G. K. & Shi, W. The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 41, e108 (2013).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012).
Frois-Martins, R. et al. Genome-guided manipulation of regulators of morphogenesis in a C. albicans strain with low virulence is not sufficient to trigger a high-virulence phenotype. Preprint at bioRxiv https://doi.org/10.1101/2025.07.16.665085 (2025).
Lemberg, C. et al. Candida albicans commensalism in the oral mucosa is favoured by limited virulence and metabolic adaptation. PLoS Pathog. 18, e1010012 (2022).
Fróis Martins, R. & LeibundGut-Landmann, S. Raw dataset associated with the publication ‘IL-17-mediated antifungal immunity restricts Candida albicans pathogenicity in the oral cavity’. Zenodo https://doi.org/10.5281/zenodo.17233074 (2025).
Gillum, A. M., Tsay, E. Y. & Kirsch, D. R. Isolation of the Candida albicans gene for orotidine-5’-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol. Gen. Genet. 198, 179–182 (1984).

















Leave a Reply