Laboratório de Immunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States.
Front Immunol. 2018 May 24;9:1128. doi: 10.3389/fimmu.2018.01128. eCollection 2018.
β integrins are critical in host defense responses to invading pathogens and inflammation. Previously, we reported that genetic deficiency of integrin αβ in mice altered outcomes in experimental systemic infections including accelerated mortality in animals infected with serovar Typhimurium. Here, we show that deficiency of αβ results in impaired accumulation of leukocytes in response to peritoneal infection by . Typhimurium, impaired pathogen clearance , defective bacterial elimination by cultured peritoneal macrophages, and enhanced pyroptosis, a cell death process triggered by . -infected animals deficient in αβ had increased levels of peritoneal cytokines in addition to other markers of pyroptosis, which may contribute to inflammatory injury and increased mortality in the context of impaired bacterial killing. These observations indicate important contributions of leukocyte integrins to the host response in experimental infection and reveal previous activities of αβ in bacterial infection.
β 整合素在宿主防御入侵病原体和炎症反应中至关重要。此前,我们报道了整合素 αβ 在小鼠中的基因缺失改变了实验性全身感染的结果,包括感染鼠伤寒沙门氏菌血清型的动物死亡率加速。在这里,我们表明 αβ 的缺乏导致对 鼠伤寒沙门氏菌腹膜感染的白细胞积累受损,病原体清除受损,培养的腹膜巨噬细胞清除细菌能力缺陷,以及细胞焦亡增加,这是一种由感染的细胞死亡过程。-缺乏 αβ 的动物除了其他焦亡标志物外,还增加了腹膜细胞因子的水平,这可能导致细菌杀伤受损时的炎症损伤和死亡率增加。这些观察结果表明白细胞整合素对实验性 感染宿主反应的重要贡献,并揭示了 αβ 在细菌感染中的先前活性。