Down-regulation of dendritic cell activation induced by Paracoccidioides brasiliensis.
Paracoccidioidomycosis (PCM) endemic in Latin America, is a progressive systemic mycosis caused by Paracoccidioides brasiliensis (Pb). The infection can evolve to different clinical forms that are associated to various degrees of suppressed cell-mediated immunity. With the recognition that DCs are able to initiate response in naïve T cells and that they also participate in Th cell education, the present study was undertaken to check whether DCs interact with P. brasiliensis, as well as to elucidate possible mechanisms and consequences of this interaction. Our results indicate that P. brasiliensis infection and purified gp43, its main antigenic component, lead to down-regulation of MHC-II and adhesion properties of immature DCs. The down-regulation was also observed in LPS-induced DC maturation. In addition, an inhibition of IL-12 and TNF-alpha production by both P. brasileinsis or gp43, was observed in LPS-induced DC maturation. These results suggest that protein, released in great amounts by the fungus, might be used, to reduce the effectiveness of the immune response.
Ferreira
Karen Spadari
KS
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Prof. Lineu Prestes, 580, Bloco 17, CEP: 05508-900, São Paulo, Brazil.
Lopes
José Daniel
JD
Almeida
Sandro Rogério
SR
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000946:Antigens, Fungal / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D015536:Down-Regulation; D005260:Female; D005656:Fungal Proteins / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008351:Mannans / Q000494:pharmacology; D051379:Mice; D010228:Paracoccidioides / Q000472:pathogenicity*; D010229:Paracoccidioidomycosis / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C103180:43 kDa protein, Paracoccidioides; D015703:Antigens, CD; D000946:Antigens, Fungal; D005656:Fungal Proteins; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D008351:Mannans; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12