O papel do receptor ST2 no controle inicial da infecção oral por Brucella abortus

Abstract

The ST2 receptor, a member of Toll-like/IL-1 receptor superfamily, is expressed in several immune cells. This receiver binds to the cytokine IL-33, that plays important functions in the gut, such as, epithelium regeneration, interaction with the microbiome, promoting intestinal homeostasis. The ST2/IL-33 axis although widely studied in the context of viral infections, its role in bacterial infections is still poorly explored.Therefore , the main goal of this study was to investigate the mechanisms involved in the process of invasion and establishment of Brucella abortus (Ba) infectionorally, exploring the role of the ST2 receptor in the intestinal microbiota and homeostasis. For this, wild-type animals Balb/c (WT) and ST2 deficient mice (ST2-/-) were infected by gavage with B.abortus and euthanized 3 and 14 days after infection (dpi). The results suggest that ST2-/- animals are more resistant to oral infection compared to WT mice, showing reduction of bacterial load in livers and spleens, with B. abortus been retained in mesenteric lymph nodes (LNM). However, this phenotype was not observed when the infection occurred via intraperitoneal route, suggesting that ST2 is important in the invasion phase of B.abortus through the intestinal mucosa. Furthermore, Ba infection induced intestinal permeability in WT mice but not in ST2-/- animals. Additionally, it was observed a lower quantity and diversity of bacterial groups present in the intestinal microbiota of ST2-/- mice when compared to WT infected animals. However, significant alterations in the composition of the intestinal microbiota was observed during infection in both animal groups, suggesting a dysbiosis phenotype; and therefore, the involvement of intestinal microbiota in the context of B. abortus infection. The infection led to an increase in the recruitment of neutrophils and eosinophils in the intestine of WT mice infected with B. abortus, a phenomena not observed in ST2-/- infected-mice. The MUC2 analysis also revealed the increase in the expression of this molecule only in the small intestine of the WT mice, suggesting that the ST2 can participate in the regulation of this molecule. On the other hand, oral infection with Ba induced higher levels of IFN-, TNF-α and IL-6 in ST2-/- mice compared to WT animals, suggesting this pro-inflammatory profile detected in the knockout mice might be related to the increased resistance observed in these animals. Our results suggest, so far, a role for ST2 receptor in the intestinal homeostasis impacting the process of Brucella abortus invasion by the intestinal mucosa and consequently, systemic dissemination after infection by the oral route.