The role of NOD1 and NOD2 receptors in the control of Leishmania (L.) major infection

Abstract

The Leishmaniasis is a spectrum of disease caused by the protozoans of the genus Leishmania that includes several species, responsible for different forms of the disease. In Brazil, the most common disease form is the cutaneous leishmaniasis that is found in almost all the national territory. Disease protection is mainly related to the assembly of Th1 immune response with production of IFN-³, which activates macrophages by inducing the synthesis of nitric oxide (NO), facilitating the elimination of intracellular parasites. The participation of pattern recognition receptors of innate immunity, such as toll-like receptors (TLR) and NOD-like receptors (NLR), to the effective induction of Th1 immune response is extremely important. Several studies have demonstrated the importance of Toll-like receptors in the induction of an efficient immune response against parasites of the genus Leishmania. However, even in the absence of these receptors is observed induction of a proinflammatory response and control of Leishmania infection, suggesting the involvement of other innate immunity receptors in the protective immune response against this parasite. Nod-like receptors, such as Nod1 and Nod2 are associated with the recognition of several classes of pathogens and immune response activation. But so far nothing has been described about the importance of these receptors in the recognition and control of infection caused by parasites of the genus Leishmania. Recently, was observed the involvement of NLRs in the induction of autophagy in response to infection with intracellular bacteria. Data from the literature and from our laboratory (unpublished) have shown that parasites of the genus Leishmania induce autophagy and its induction depends on the activation of the Nod/Rip2 pathway. Besides the already known functions of autophagy, studies have shown that this process is directly related to antigen presentation and subsequent activation of T lymphocytes. In this context, this work aims to assess the role of Nod1 and Nod2 receptors and their adapter molecule RIP2 in the control of infection induced by L. major and to investigate the role of these signaling pathways in the induction of adaptive immune response during the infection. Additionally, we intend to analyze the role of Nod1 and Nod2 receptors in the antigen presentation, dependent of autophagy process, during infection by L. major. (AU)