A IL-18 no desenvolvimento de lesões cutâneas na infecção por Leishmania amazonensis e inflamação induzida pela λ-Carragenina

Abstract

In infection by Leishmania amazonensis the classic model of polarization Th1 and Th2, found in the model of infection with Leishmania major, does not apply. What is described is a mixture of the profiles Th1, Th2, Treg and Th17. The IL-18 is a pro-inflammatory cytokine that has a capability to polarizes T lymphocytes to Th1, Th17 and Th2 phenotypes, depending on the environment in which it finds. Our work aims to identify the role of the IL-18 in the course of infection and development of skin lesions in mice infected by L. amazonensis. Our data showed that the IL-18 KO mice have a smaller lesion than the wild-type animals (C57BL/6) since the beginning of the infection. In addition, the times analyzed, the two strains have the same parasite burden when infected with 102,104 and 105 promastigotes forms of L. amazonensis. On the cytokine profile, we found considerable levels of IL-12, TNF in both strains, but we found higher levels of IL-10 in the KO mice. During the course of infection we identified a massive percentage of T cells CD4+ expressing the receptor for IL-18 after the fourth week of infection. This coincides with the appearance of the lesion exacerbated in wt mice and can be associated with the peak production of IL-18 seen by ELISA. We treat the mice KO and wt, with antiCD4(GK1.5) and we also look the profile of activation of the CD4+ T cells before, during and after the treatment with GK.1.5. To validade our hypothesis, we infected the IL-18 KO mice and treated these animals with CD4+ T cells from a wt GFP+ mice. Our data suggests that the IL-18 is partially involved in susceptibility to infection by L. amazonensis. This is likely due to the interaction of IL-18 on T lymphocytes helping the maintenance of the lesion. In other model like the inflammation induced by carrageenan, the IL-18 KO mice has also a smaller lesion in comparison to the lesion of the wild-type mice. An interesting fact was that inflammatory cells, such as macrophages and monocytes, that did not present expression of IL-18 receptor during infection by L. amazonensis began to express in the model of carrageenan-induced inflammation. Our data indicate that IL-18 is involved in increasing of lesions, both in the models of inflammation in L. amazonensis infection and in carrageenan-induced inflammation.