Absence of CD4+ T cells impairs host defence of mice infected with Fonsecaea pedrosoi.

Chromoblastomycosis is a human chronic, often debilitating, suppurative, granulomatus mycosis of the skin and subcutaneous tissues beginning after inoculation trauma. It occurs worldwide, but is more frequently observed in tropical countries such as Brazil. Some studies have focused on fungus-host interaction, showing a predominantly cell-mediated immune response, with the activation of macrophages involved in fungus phagocytosis. Immunization with live conidia produced a high influx of CD4 T cells into the draining lymph node. The sensitized T cells proliferate in vitro when restimulated with specific antigen and preferentially produce IFN- gamma. To better characterize the role played by T cells on the chromoblastomycosis infection we used mice deficient for CD4 and CD8. Data determined by CFU counts associated with decreased DTH and IFN-gamma production of infected mice clearly demonstrated that, during experimental F. pedrosoi infection, absence of CD4(+) cells induces a more severe disease.

Phagocytosis, production of nitric oxide and pro-inflammatory cytokines by macrophages in the presence of dematiaceous [correction of dematiaceus] fungi that cause chromoblastomycosis.

Chromoblastomycosis is characterized by the slow development of polymorphic skin lesions (nodules, verrucas, tumores, plaques and scar tissue). Inside the host, infectious propagules adhere to epithelial cells and differentiate into sclerotic forms, which effectively resist destruction by host effector cells and allow onset of chronic disease. A cellular immune response against fungi is essential to control infection. Amongst the cells of the immune system, macrophages play the most important role in controlling fungal growth. In this study, we show that the fungicidal characteristic of macrophages is dependent on the fungal species that causes chromoblastomycosis. We began by observing that the phagocytic index was higher for Fonsecaea pedrosoi and Rhinocladiella aquaspersa compared with that of other fungi. Complement-mediated phagocytosis was more important for Phialophora verrucosa and R. aquaspersa and was inhibited by mannan when F. pedrosoi and R. aquaspersa conidia were phagocytosed by macrophages. We showed that macrophages killed significantly only R. aquaspersa. We also found that the phagocytosis of fungi has functional consequences for macrophages as phagocytosis resulted in down-modulation of MHC-II and CD80 expression as well as in the inhibition of the basal liberation of NO. However, the inhibition of the basal liberation of NO nor the down-modulation of MHC and co-stimulatory molecules were observed in the presence of R. aquaspersa.