Avaliação do papel da Galectina-3 na infecção pela bactéria intracelular Brucella abortus

Abstract

Brucella abortus is a Gram-negative bacterium, facultative intracellular pathogen, which causes undulant fever and arthritis in humans and infertility in animals, resulting in serious economic losses. Brucella pathogenesis is associated with the bacteria replication efficiency in the host dendritic cells and macrophages. B. abortus lives in vacuoles termed Brucella containing vacuoles (BCVs) localized inside phagocytes. Innate immune response against B. abortus involves the activation of several pathogen recognition receptors in the antigen presenting cells (APCs). Galectins are a group of proteins characterized by the ability to bind pathogens and modulate the immune response. Recently, different roles have been related to Gal-3 in the immune response, such as the direct interaction with pathogens surface glycans and regulation of inflammatory events, like cytokines production. However, the role of Gal-3 during B. abortus infection has not yet been investigated. The aim of this study was to evaluate the role of Gal-3 during B. abortus infection. Our findings indicate that Gal-3 is dispensable for Brucella-containing vacuoles disruption, inflammasome activation and pyroptosis. On the other hand, we observed that Brucella-induced Gal-3 expression is crucial for induction of molecules associated to type I IFN signaling pathway, such as Interferon beta (IFN-β), C-X-C motif chemokine ligand 10 (CXCL10) and guanylate-binding proteins (GBPs). Gal-3 KO macrophages showed reduced bacterial numbers compared to wild-type cells, suggesting that Gal-3 facilitates bacterial replication in vitro. Moreover, priming Gal-3 KO cells with IFN-β favored B. abortus survival in macrophages. Additionally, we also observed that Gal-3 KO mice are more resistant to B. abortus infection and these animals showed elevated production of proinflammatory cytokines when compared to control mice. Finally, we observed an increased recruitment of macrophages, dendritic cells and neutrophils in spleens of Gal-3 KO mice compared to wild-type animals. In conclusion, this study demonstrated that Brucella-induced Gal-3 is detrimental to host and this molecule is implicated in inhibition of recruitment and activation of immune cells, which promotes B. abortus spread and aggravates the infection.