Epidermal clearance of<i>Candida albicans</i>is mediated by IL-17 but independent of fungal innate immune receptors
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- Mari T Iwasawa
- Department of Dermatology, Graduate School of Medicine, Chiba University , Chiba-shi, Chiba 260-8670 , Japan
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- Hideaki Miyachi
- Department of Dermatology, Graduate School of Medicine, Chiba University , Chiba-shi, Chiba 260-8670 , Japan
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- Seiichiro Wakabayashi
- Department of Dermatology, Graduate School of Medicine, Chiba University , Chiba-shi, Chiba 260-8670 , Japan
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- Takashi Sugihira
- Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University , Suita-shi, Osaka 565-0871 , Japan
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- Reika Aoyama
- Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University , Suita-shi, Osaka 565-0871 , Japan
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- Seitaro Nakagawa
- Department of Dermatology, Graduate School of Medicine, Chiba University , Chiba-shi, Chiba 260-8670 , Japan
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- Yuki Katayama
- Department of Dermatology, Graduate School of Medicine, Chiba University , Chiba-shi, Chiba 260-8670 , Japan
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- Mitsutoshi Yoneyama
- Division of Molecular Immunology, Medical Mycology Research Center, Chiba University , Chiba-shi, Chiba 260-8673 , Japan
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- Hiromitsu Hara
- Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima-shi, Kagoshima 890-8544 , Japan
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- Yoichiro Iwakura
- Division of Molecular Immunology, Medical Mycology Research Center, Chiba University , Chiba-shi, Chiba 260-8673 , Japan
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- Masanori Matsumoto
- Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109 , USA
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- Naohiro Inohara
- Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109 , USA
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- Hanako Koguchi-Yoshioka
- Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University , Suita-shi, Osaka 565-0871 , Japan
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- Manabu Fujimoto
- Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University , Suita-shi, Osaka 565-0871 , Japan
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- Gabriel Núñez
- Department of Pathology, University of Michigan Medical School , Ann Arbor, MI 48109 , USA
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- Hiroyuki Matsue
- Department of Dermatology, Graduate School of Medicine, Chiba University , Chiba-shi, Chiba 260-8670 , Japan
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- Yuumi Nakamura
- Department of Dermatology, Graduate School of Medicine, Chiba University , Chiba-shi, Chiba 260-8670 , Japan
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- Shinobu Saijo
- Division of Molecular Immunology, Medical Mycology Research Center, Chiba University , Chiba-shi, Chiba 260-8673 , Japan
説明
<jats:title>Abstract</jats:title><jats:p>Abstract</jats:p><jats:p>IL-17 plays important roles in host defense against Candida albicans at barrier surfaces and during invasive infection. However, the role of IL-17 in host defense after colonization of the epidermis, a main site of C. albicans infection, remains poorly understood. Using a murine model of epicutaneous candidiasis without skin abrasion, we found that skin inflammation triggered by epidermal C. albicans colonization was self-limiting with fungal clearance completed by day 7 after inoculation in wild-type mice or animals deficient in IL-17A or IL-17F. In contrast, marked neutrophilic inflammation in the epidermis and impaired fungal clearance were observed in mice lacking both IL-17A and IL-17F. Clearance of C. albicans was independent of Dectin-1, Dectin-2, CARD9 (caspase-recruitment domain family, member 9), TLR2 (Toll-like receptor 2) and MyD88 in the epidermal colonization model. We found that group 3 innate lymphoid cells (ILC3s) and γδT cells were the major IL-17 producers in the epicutaneous candidiasis model. Analyses of Rag2−/− mice and Rag2−/−Il2rg−/− mice revealed that production of IL-17A and IL-17F by ILC3s was sufficient for C. albicans clearance. Finally, we found that depletion of neutrophils impaired C. albicans clearance in the epidermal colonization model. Taken together, these findings indicate a critical and redundant function of IL-17A and IL-17F produced by ILC3s in host defense against C. albicans in the epidermis. The results also suggest that epidermal C. albicans clearance is independent of innate immune receptors or that these receptors act redundantly in fungal recognition and clearance.</jats:p>
収録刊行物
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- International Immunology
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International Immunology 34 (8), 409-420, 2022-05-31
Oxford University Press (OUP)