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

doi:10.1371/journal.pntd.0006237

CORC > 武汉植物园 > 中国科学院武汉植物园

	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
	Tong, Zhongsheng 1; Li, Ruoyu 2; Chen, Sharon C. -A.3; Liu, Weihuang 4; Liu, Wei 5; Chen, Yao 1; Zhang, Xu 1; Duan, Yiqun 1; Li, Dongsheng 1; Chen, Liuqing 1
刊名	PLOS NEGLECTED TROPICAL DISEASES
	2018-02-01
卷号	12 期号:2 页码:31
ISSN号	1935-2735
DOI	10.1371/journal.pntd.0006237
英文摘要	Fonsecaea 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.
资助项目	National Natural Science Foundation of China[81301376] ; National Natural Science Foundation of China[81573062]
WOS研究方向	Infectious Diseases ; Parasitology ; Tropical Medicine
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000427279700030
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/4840]
专题	中国科学院武汉植物园
通讯作者	Li, Dongsheng; Chen, Liuqing
作者单位	1.1 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
推荐引用方式 GB/T 7714	Tong, Zhongsheng,Li, Ruoyu,Chen, Sharon C. -A.,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	Tong, Zhongsheng.,Li, Ruoyu.,Chen, Sharon C. -A..,Liu, Weihuang.,Liu, Wei.,...&Dong, Bilin.(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	Tong, Zhongsheng,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.