Novas abordagens sobre a imubiologia da ascardíase larval

Abstract

Studies related to the immunobiological aspects of an Ascaris spp. infection are still scarce, especially those that aim to elucidate the early events of the immune response. In this study, we demonstrated a novel standardized method for early experimental Ascaris infection, using a murine model, and we evaluated the main aspects about the lung immunopathology induced by the Ascaris larvae migration. Besides that, the innate immune response, highlighting the role of eosinophils in the control of parasitic burden and into the pathogenesis of lung inflammation was evaluated, using an eosinophil-deficient mice model (dblGATA mice). Finally, a coinfection model by respiratory Vaccinia virus (VACV) and pulmonary ascariasis was performed in order to evaluate the impact of Ascaris larvae migration through an inflammatory microenvironment, and to evaluate the capacity of larval ascariasis on alter the course of viral infection. The main findings of this study suggest that the protective immunity against larval ascariasis is mediated by an intense innate inflammatory response, characterized by the activation of eosinophils by IL-5 producing innate lymphoid cells. These eosinophils are responsible to potentiate the innate immunity, activating neutrophils, which produce IL-6 and MPO, increasing the lung inflammation. This lung inflammation decreases the number of migrating larvae, however causes tissue damage and fibrosis. To restore lung homeostasis, eosinophils start to produce TNF and EPO, which are involved in the lung remodeling and repairing after larvae migration. This hypothesis on the mechanisms of protection against larval ascariasis was supported by the experiments of coinfection with VACV and A. suum. The results revealed that the increase of lung inflammation induced by the airway concomitant infection was responsible to reduce consistently the number of migrating larvae through the lungs of coinfected mice. Taken together, the novel aspects of Ascaris infection presented here enabled a better understanding of the immunopathological events during larval migration, providing insight for further studies focused on immunization and immunoprophylatic assays.