O papel da proteína cinase 4 associada ao receptor de interleucina 1 (irak4) na infecção pelo parasito: Toxoplasma gondii

Abstract

A kinase associated with the interleukin 4 receptor 1 (IRAK4) and a member of the IRAK family with an important role in the production of inflammatory mediators. This kinase and subsequent the adapter molecule MyD88 signaling pathway of receptors vToll (TLR). Toxoplasmosis and an important zoonosis that affects about a third of the world's population with serious consequences for immunosuppressed individuals and for congenital disease. The production of inflammatory mediators is essential for host resistance to infection by T. gondii, and individuals deficient IRAK4 the molecule, so as human murine model become interesting To investigate the role of this molecule during infection. Thus, in we investigate the role of kinase IRAK4 during oral infection deficient animals and controls, with the ME49 strain of T. gondii. Animals IRAK4 - / - showed high morbidity, weight loss, parasitism and accelerated mortality when compared with control animals. Histopathological analysis showed that animals deficient brain showed numerous foci of necrosis associated with the parasite and the absence of perivascular inflammatory infiltrate. splenic evaluation showed a significant reduction of the follicles and germinal centers in infected animals deficient, corroborating the reduced B cell number activated with proliferative capacity these same animals as well as in T lymphocytes producing IFN. Furthermore, both the number of monocytes / macrophages and dendritic cells (DCs) as well as cytokine production (IL - 12 and TNFá) and expression of activation molecules by these cells were also affected by infection-deficient animals. Resistance to infection was restored when infected deficient animals were treated in vivo with recombinant IL-- 12. Interestingly, in humans, we observed a significant association of polymorphisms present in IRAK4 gene (rs1461567 and rs4251513, p <0.023 and p <0.045, respectively) with congenital heart disease in individuals affected by eye and / or brain damage. Thus, IRAK4 signaling pathway is essential for the activation of cells of innate immunity and acquired immunity developing effector host resistance to infection by T. gondii.