title: A chitin-like component on sclerotic cells of Fonsecaea pedrosoi inhibits Dectin-1-mediated murine Th17 development by masking β-glucans.
abstract: Fonsecaea pedrosoi (F. pedrosoi), a major agent of chromoblastomycosis, has been shown to be recognized primarily by C-type lectin receptors (CLRs) in a murine model of chromoblastomycosis. Specifically, the β-glucan receptor, Dectin-1, mediates Th17 development and consequent recruitment of neutrophils, and is evidenced to have the capacity to bind to saprophytic hyphae of F. pedrosoi in vitro. However, when embedded in tissue, most etiological agents of chromoblastomycosis including F. pedrosoi will transform into the sclerotic cells, which are linked to the greatest survival of melanized fungi in tissue. In this study, using immunocompetent and athymic (nu/nu) murine models infected subcutaneously or intraperitoneally with F. pedrosoi, we demonstrated that T lymphocytes play an active role in the resolution of localized footpad infection, and there existed a significantly decreased expression of Th17-defining transcription factor Rorγt and inefficient recruitment of neutrophils in chronically infected spleen where the inoculated mycelium of F. pedrosoi transformed into the sclerotic cells. We also found that Dectin-1-expressing histocytes and neutrophils participated in the enclosure of transformed sclerotic cells in the infectious foci. Furthermore, we induced the formation of sclerotic cells in vitro, and evidenced a significantly decreased binding capacity of human or murine-derived Dectin-1 to the induced sclerotic cells in comparison with the saprophytic mycelial forms. Our analysis of β-glucans-masking components revealed that it is a chitin-like component, but not the mannose moiety on the sclerotic cells, that interferes with the binding of β-glucans by human or murine Dectin-1. Notably, we demonstrated that although Dectin-1 contributed to the development of IL-17A-producing CD3+CD4+ murine splenocytes upon in vitro-stimulation by saprophytic F. pedrosoi, the masking effect of chitin components partly inhibited Dectin-1-mediated Th17 development upon in vitro-stimulation by induced sclerotic cells. Therefore, these findings extend our understanding of the chronicity of chromoblastomycosis.
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Bilin
authors.initials: B
authors.lastname: Dong
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Li
authors.affiliation: Research Center for Medical Mycology, Peking University, Beijing, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Li
authors.affiliation: Center for Infectious Diseases and Microbiology, Laboratory Services, ICPMR-Pathology West, Westmead Hospital, University of Sydney, Westmead, Australia.
authors.forename: Sharon C-A
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Medical Research Center of Wuhan University, Wuhan, China.
authors.forename: Weihuang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xia
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No. 1 Hospital of Wuhan, Wuhan, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D001203:Ascomycota / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D039521:CD11c Antigen / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects; D002686:Chitin / Q000737:chemistry / Q000494:pharmacology*; D002862:Chromoblastomycosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007121:Immunocompetence; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D013154:Spleen / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D047071:beta-Glucans / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D039521:CD11c Antigen; D002686:Chitin; D006861:Hydrogen Peroxide; D037181:Lectins, C-Type; D047071:beta-Glucans; D000099181:Dectin-1