The intraspecies diversity of C. albicans triggers qualitatively and temporally distinct host responses that determine the balance between commensalism and pathogenicity.
The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory neutrophil response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host responses. Altogether, this study provides a comprehensive understanding of the antifungal response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal-host interactions in vivo.
Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.|Laboratory of Applied Microbiology, DACD, SUPSI, Bellinzona, Switzerland.
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Schönherr
Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
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Sparber
Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
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Kirchner
Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
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Guiducci
Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
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Trautwein-Weidner
Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
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Gladiator
Institut Pasteur, INRA, Unité Biologie et Pathogénicité Fongiques, Paris, France.
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Sertour
Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
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Hetzel
Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
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Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
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Pavelka
Institut Pasteur, INRA, Unité Biologie et Pathogénicité Fongiques, Paris, France.
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d'Enfert
Institut Pasteur, INRA, Unité Biologie et Pathogénicité Fongiques, Paris, France.|Unité de Parasitologie-Mycologie, Service de Microbiologie clinique, Hôpital Necker-Enfants-Malades, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
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Bougnoux
Laboratory of Applied Microbiology, DACD, SUPSI, Bellinzona, Switzerland.
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Corti
Section of Immunology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
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LeibundGut-Landmann
D000067531:Alarmins / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D044822:Biodiversity; D002176:Candida albicans / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology*; D002460:Cell Line; D002465:Cell Movement; D054884:Host-Pathogen Interactions; D006801:Humans; D018928:Immunity, Mucosal; D020381:Interleukin-17 / Q000378:metabolism; D015603:Keratinocytes / Q000382:microbiology / Q000502:physiology*; D009061:Mouth Mucosa / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology*; D015398:Signal Transduction; D013045:Species Specificity; D013559:Symbiosis; D014774:Virulence
D000067531:Alarmins; D001426:Bacterial Proteins; D020381:Interleukin-17