Characterization of the immunological mechanisms associated with the protective and deleterious effects of nitric oxide in pulmonary paracoccidioidomycosis. / Caracterização dos mecanismos imunológicos associados com os efeitos protetores e deletérios do óxido nitrico na Paracoccidioidomicose pulmonar.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Paracoccidioidomycosis is acquired by the respiratory route and nitric oxide (NO) is involved in the killing of pathogens, we aimed to investigate the role of NO in the course of the disease using NO- synthase deficient (iNOS-/-) and WT mice. At week 2 postinfection, NO absence resulted in less severe infection associated with increased TNF-a levels besides a massive influx of activated T cells and macrophages to the lungs. By week 10, iNOS-/- mice developed increased fungal burdens allied with less pronounced influx of activated T cells and macrophages and increased presence of regulatory CD4+CD25+FoxP3+ T cells to the lungs. Only iNOS-/- mice developed organized pulmonary granulomas, although no differences in the mortality rates were detected. The differences in the morphology of lesions were partially abrogated by TNF-a depletion which, induced a precocious mortality of iNOS-/- and massive influx of inflammatory pulmonary cells. Indeed, the CD8+T cells depletion developed a more severe infection with less recruitment of pulmonary cells in iNOS-/- mice.

ASSUNTO(S)

imunologia cytokines immunology paracoccidioidomicose linfócitos macrophages lymphocytes macrófagos Óxido nítrico granuloma paracoccidioidomycosis granuloma citocinas nitric oxide

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