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Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-gamma production
Dong, Bilin1; Tong, Zhongsheng1; Li, Ruoyu2; Chen, Sharon C. -A.3; Liu, Weihuang4; Liu, Wei5; Chen, Yao1; Zhang, Xu1; Duan, Yiqun1; Li, Dongsheng1; Chen, Liuqing1
Corresponding AuthorLi, Dongsheng(dongshengli1975@126.com) ; Chen, Liuqing(chenlq1974@126.com)
2018-02-01
Source PublicationPLOS NEGLECTED TROPICAL DISEASES
ISSN1935-2735
Volume12Issue:2Pages:31
AbstractFonsecaea pedrosoi (F. pedrosoi) is the most common agent of chromoblastomycosis. Transformation of this fungus from its saprophytic phase into pathogenic sclerotic cells in tissue is an essential link to the refractoriness of this infection. Experimental studies in murine models have shown that the absence of CD4+ T cells impairs host defense against F. pedrosoi infection. Clinical research has also suggested that a relatively low level of the Th1 cytokine INF-gamma and inefficient T cell proliferation are simultaneously present in patients with severe chromoblastomycosis upon in vitro stimulation with ChromoAg, an antigen prepared from F. pedrosoi. In the present study, we show that in mice intraperitoneally infected with F. pedrosoi-spores, -hyphae or in vitro-induced sclerotic cells respectively, the transformation of this causative agent into sclerotic cells contributes to a compromised Th1 cytokine production in the earlier stage of infection with impaired generation of neutrophil reactive oxygen species (ROS) and pan-inhibition of Th1/Th2/Th17 cytokine production with disseminated infection in the later stage by using a CBA murine Th1/Th2/Th17 cytokine kit. In addition, we have further demonstrated that intraperitoneal administration of recombinant mouse IFN-gamma (rmIFN-gamma) effectively reduces the fungal load in the infected mouse spleen, and dampens the peritoneal dissemination of F. pedrosoi-sclerotic cells. Meanwhile, exogeneous rmIFN-gamma contributes to the formation and maintenance of micro-abscess and restores the decrease in neutrophil ROS generation in the mouse spleen infected with F. pedrosoisclerotic cells. Of note, we have once again demonstrated that it is a chitin-like component, but not beta-glucans or mannose moiety, that exclusively accumulates on the outer cell wall of F. pedrosoi-sclerotic cells which were induced in vitro or isolated from the spleens of intraperitoneally infected BALB/c mice. In addition, our results indicate that decreased accumulation of chitin on the surface of live F. pedrosoi-sclerotic cells after chitinase treatment can be self-compensated in a time-dependent manner. Importantly, we have for the first time demonstrated that exclusive accumulation of chitin on the transformed sclerotic cells of F. pedrosoi is involved in an impaired murine Th1 cytokine profile, therefore promoting the refractoriness of experimental murine chromoblastomycosis.
DOI10.1371/journal.pntd.0006237
Funding OrganizationNational Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
Indexed BySCI ; SCI
Language英语
Funding ProjectNational Natural Science Foundation of China[81301376] ; National Natural Science Foundation of China[81573062]
WOS Research AreaInfectious Diseases ; Parasitology ; Tropical Medicine
WOS SubjectInfectious Diseases ; Parasitology ; Tropical Medicine
WOS IDWOS:000427279700030
WOS KeywordIN-VITRO ; FORMS ; WALL ; CYTOKINES ; INFECTION ; YEAST ; PROLIFERATION ; ARCHITECTURE ; MACROPHAGES ; NEUTROPHILS
PublisherPUBLIC LIBRARY SCIENCE
Funding OrganizationNational Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
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Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/29716
Collection其他_期刊论文
Corresponding AuthorLi, Dongsheng; Chen, Liuqing
Affiliation1.1 Hosp Wuhan, Dept Dermatol, Ctr Infect Skin Dis, Wuhan, Hubei, Peoples R China
2.Peking Univ, Res Ctr Med Mycol, Beijing, Peoples R China
3.Univ Sydney, Westmead Hosp, ICPMR, Lab Serv,Ctr Infect Dis & Microbiol, Westmead, NSW, Australia
4.Wuhan Univ, Med Res Ctr, Wuhan, Hubei, Peoples R China
5.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Dong, Bilin,Tong, Zhongsheng,Li, Ruoyu,et al. Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-gamma production[J]. PLOS NEGLECTED TROPICAL DISEASES,2018,12(2):31.
APA Dong, Bilin.,Tong, Zhongsheng.,Li, Ruoyu.,Chen, Sharon C. -A..,Liu, Weihuang.,...&Chen, Liuqing.(2018).Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-gamma production.PLOS NEGLECTED TROPICAL DISEASES,12(2),31.
MLA Dong, Bilin,et al."Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-gamma production".PLOS NEGLECTED TROPICAL DISEASES 12.2(2018):31.
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