Stimulation, inhibition and death of macrophages infected with Trichophyton rubrum.
Trichophyton rubrum is the most common pathogen causing dermatophytosis, accounting for approximately 80% of the reported cases of onychomycosis. Since 90% of the chronic dermatophyte infections are caused by T. rubrum, it is likely that this pathogen must have evolved mechanisms that evade or suppress cell-mediated immunity. Several reports have highlighted the participation of phagocytes in the immune defense against fungi; however, few studies have addressed the role of these cells in dermatophytosis. In this study, we investigated the interactions of resident and peritoneal macrophages with T. rubrum. We show here that the interaction of T. rubrum conidia with resident macrophages results in the production of TNF-alpha and IL-10 but not IL-12 and nitric oxide. Infected macrophages down-regulated the expression of co-stimulatory molecules (CD80 and CD54). We also show that phagocytosis of T. rubrum conidia is inhibited by the addition of fungal exoantigens or mannan. Cytotoxicity assays indicated that after 8 h of conidia ingestion macrophage viability decreased drastically. Electron microscopy revealed that the ingested conidia grow and differentiate into hyphae inside macrophages leading to rupture of the macrophage membrane.
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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.
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Gomes
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D000818:Animals; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology; D051379:Mice; D010587:Phagocytosis; D014249:Trichophyton / Q000254:growth & development / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10