Santos Raiany A, Cerqueira Daiane M, Zamboni Dario S, Oliveira Sergio C
Departamento de Genética, Ecologia e Evolução, Programa de Pós-Graduação em Genética, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Front Microbiol. 2022 Dec 1;13:1086925. doi: 10.3389/fmicb.2022.1086925. eCollection 2022.
Programmed cell death (PCD) is an important mechanism of innate immunity against bacterial pathogens. The innate immune PCD pathway involves the molecules caspase-7 and caspase-8, among others. 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 studies so far have revealed the role of caspase-7 or caspase-8 during this bacterial infection. Herein, we demonstrate that caspase-7 is dispensable for caspase-1 processing, IL-1β secretion and cell death in macrophages. Additionally, caspase-7 deficient animals control infection as well as the 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 KO macrophages showed reduced LDH release when compared to wild type, suggesting that caspase-8 may play an important role in pyroptosis in response to . Finally, caspase-8 KO animals were more susceptible to 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 infection.
程序性细胞死亡（PCD）是机体抵御细菌病原体的固有免疫的重要机制。固有免疫PCD途径涉及多种分子，其中包括半胱天冬酶-7（caspase-7）和半胱天冬酶-8（caspase-8）。布鲁氏菌是一种革兰氏阴性菌，可引发人畜共患疾病——布鲁氏菌病。针对这种病原体的固有免疫反应涉及炎性小体成分的激活和细胞焦亡的诱导。然而，迄今为止尚无研究揭示caspase-7或caspase-8在这种细菌感染过程中的作用。在此，我们证明caspase-7对于巨噬细胞中caspase-1的加工、白细胞介素-1β（IL-1β）的分泌及细胞死亡并非必需。此外，caspase-7缺陷型动物对布鲁氏菌感染的控制能力与野生型小鼠相当。此外，我们探讨了caspase-8在这种细菌感染过程中炎性小体激活和细胞焦亡中的作用。与野生型细胞相比，caspase-8缺陷的巨噬细胞分泌的IL-1β量减少，这与caspase-1活性降低相一致。此外，与野生型相比，caspase-8基因敲除（KO）的巨噬细胞乳酸脱氢酶（LDH）释放减少，这表明caspase-8可能在对布鲁氏菌感染的细胞焦亡中起重要作用。最后，与野生型小鼠相比，caspase-8 KO动物对布鲁氏菌感染更易感。总体而言，本研究有助于更好地理解caspase-7和caspase-8在抵御布鲁氏菌感染的固有免疫中的作用。
