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

• Ano de defesa: 2023
• Autor(a) principal: Raiany Araujo Santos
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; Programa de Pós-Graduação em Genética; UFMG
• Palavras-chave em Português: Caspase-8; Caspase-7; Brucella abortus; inflamassoma; piroptose; imunidade inata; Genética; Caspase 8; Caspase 7; Inflamassomos; Piroptose; Imunidade Inata
• Link de acesso: http://hdl.handle.net/1843/59608

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.