O Papel da caspase-8 no controle da infecção causada pela bactéria intracelular Brucella abortus

Abstract

Programmed cell death (PCD) is an important mechanism of innate immunity against bacterial pathogens. The PCD innate imune response involves the molecules caspase-7 and caspase-8, among others. Brucella abortus is a Gram-negative bacterium that causes a zoonotic disease termed brucellosis. The innate immune response against this pathogen involves activation of inflammasome components and induction of pyroptosis. However, no study has revealed the role of caspase-7 or caspase-8 during this bacterial infection. Here, we demonstrate that caspase-7 is dispensable for caspase-1 processing, IL-1β secretion and cell death in macrophages. Animals deficient in caspase-7 have been shown to control B. abortus infection as well as wild type mice. Furthermore, we addressed the role of caspase-8 in inflammasome activation and pyroptosis during this bacterial infection. Macrophages deficient in caspase-8 secreted reduced amounts of IL-1β that parallels with diminished caspase-1 activity when compared to wild type cells. Additionally, caspase-8 deficient macrophages showed reduced LDH release and gasdermin-D (GSDMD) cleavage when compared to wild type, suggesting that caspase-8 may play an important role in pyroptosis in response to B. abortus. Finally, caspase-8 deficient animals were more susceptible to Brucella infection when compared to wild type mice. Overall, this study contributes to a better understanding of the involvement of caspase-7 and caspase-8 in innate immunity against B. abortus infection.