The effects of nitric oxide on the immune system during Trypanosoma cruzi infection

• Autor(a) principal: Gutierrez,Fredy RS
• Data de Publicação: 2009
• Outros Autores: Mineo,Tiago WP, Pavanelli,Wander R, Guedes,Paulo MM, Silva,João S
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Memórias do Instituto Oswaldo Cruz
• Texto Completo: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762009000900030
• topic: Trypanosoma cruzi; nitric oxide; myocarditis; cytokines; regulatory T cells

Trypanosoma cruzi infection triggers substantial production of nitric oxide (NO), which has been shown to have protective and toxic effects on the host's immune system. Sensing of trypomastigotes by phagocytes activates the inducible NO-synthase (NOS2) pathway, which produces NO and is largely responsible for macrophage-mediated killing of T. cruzi. NO is also responsible for modulating virtually all steps of innate and adaptive immunity. However, NO can also cause oxidative stress, which is especially damaging to the host due to increased tissue damage. The cytokines IFN-³ and TNF-±, as well as chemokines, are strong inducers of NOS2 and are produced in large amounts during T. cruzi acute infection. Conversely, TGF-² and IL-10 negatively regulate NO production. Here we discuss the recent evidence describing the mechanisms by which NO is able to exert its antimicrobial and immune regulatory effects, the mechanisms involved in the oxidative stress response during infection and the implications of NO for the development of therapeutic strategies against T. cruzi.