Transformation of < i > Fonsecaea pedrosoi < /i > into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN- γ production

by Bilin Dong, Zhongsheng Tong, Ruoyu Li, Sharon C.-A. Chen, Weihuang Liu, Wei Liu, Yao Chen, Xu Zhang, Yiqun Duan, Dongsheng Li, Liuqing ChenFonsecaea 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 againstF.pedrosoi infection. Clinical research has also suggested that a relatively low level of the Th1 cytokine INF- γ and inefficient T cell proliferation are simultaneously present in patients with severe chromoblastomycosis upon in vitro stimulation with ChromoAg, an antigen prepared fromF.pedrosoi. In the present study, we show that in mice intraperitoneally infected withF.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- γ (rmIFN-γ) effectively reduces the fungal load in the infected mouse spleen, ...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research