Papel de socs-2 e da enzima 5-lo durante a infecção experimental por Trypanosoma Cruzi: alteração da microbiota e proteção intestinal

Abstract

The Chagas disease caused by the protozoan Trypanosoma cruzi, being a disease that has a higher incidence in Latin American countries, ends up becoming neglected. The big problem with this disease is that in the chronic phase the cure rate is very low, with cardiac (20-30%) and / or digestive (10-15%) complications. Studies have demonstrated the importance of lipid mediators in the face of parasitic infections regulating the homeostasis of the host organism. The intestinal microbiota is described in the literature as one of the main pillars of the adaptive immune response and that communicates with several systems such as the central nervous system and the respiratory system. In this work, our objective was to elucidate the role of the cytokine signaling suppressor protein (SOCS) - 2 and the enzyme 5-lipoxygenase (LO) during experimental infection by T. cruzi mainly in altering the intestinal microbiota composition against this disease. To carry out the experiment we used knockout mice (KO) for our target proteins. The animals were infected or not intraperitoneally with 1000 trypomastigote forms of the Y strain of T. cruzi. The 5-LO deficiency favored an increase in parasitemia during the 5th and 7th dpi compared to its wild group (WT), while SOCS-2 did not have the same difference, suggesting that the 5-LO enzyme plays an important role during the answer against T. cruzi. The infected animals of all groups started to have a very significant weight loss from the 7th dpi, during the peak of the parasitemia, the mortality rate was higher in the SOCS2 KO animals, but not in the 5-LO KO, infected in compared to WT. Regarding the microbiota, the presence of the enzyme 5-LO and the absence of SOCS-2 favored the expansion of enterobacteria, indicative of dysbiosis of the intestinal microbiota. The absence of SOCS-2 results in increased intestinal colon inflammation during infection. Collectively our data suggest that the enzyme 5-LO and SOCS-2 plays an important role during infection by T. cruzi, controlling the expansion of enterobacteria, and that the SOCS-2 protein is essential in protecting against intestinal/colon damage.