Segovia Jesus A, Chang Te-Hung, Winter Vicki T, Coalson Jacqueline J, Cagle Marianna P, Pandranki Lavanya, Bose Santanu, Baseman Joel B, Kannan Thirumalai R
Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Infect Immun. 2017 Dec 19;86(1). doi: 10.1128/IAI.00548-17. Print 2018 Jan.
is an atypical bacterial respiratory pathogen known to cause a range of airway inflammation and lung and extrapulmonary pathologies. We recently reported that an -derived ADP-ribosylating and vacuolating toxin called community-acquired respiratory distress syndrome (CARDS) toxin is capable of triggering NLRP3 (NLR-family, leucine-rich repeat protein 3) inflammasome activation and interleukin-1β (IL-1β) secretion in macrophages. However, it is unclear whether the NLRP3 inflammasome is important for the immune response during acute infection. In the current study, we utilized and models of infection to characterize the role of the NLRP3 inflammasome during acute infection. infected macrophages deficient for inflammasome components NLRP3, ASC (apoptosis speck-like protein containing a caspase activation and recruitment domain), or caspase-1 failed to process and secrete IL-1β. The MyD88/NF-κB signaling pathway was found to be critical for proinflammatory gene expression in macrophages infected with C57BL/6 mice deficient for NLRP3 expression were unable to produce IL-1β in the airways during acute infection, and lack of this inflammatory response led to deficient immune cell activation and delayed bacterial clearance. These findings are the first to report the importance of the NLRP3 inflammasome in regulating the inflammatory response and influencing the progression of during acute infection.
是一种非典型细菌呼吸道病原体，已知可引起一系列气道炎症以及肺部和肺外病变。我们最近报道，一种名为社区获得性呼吸窘迫综合征（CARDS）毒素的ADP核糖基化和空泡化毒素能够触发巨噬细胞中NLRP3（NLR家族富含亮氨酸重复序列蛋白3）炎性小体激活和白细胞介素-1β（IL-1β）分泌。然而，尚不清楚NLRP3炎性小体在急性感染期间的免疫反应中是否重要。在本研究中，我们利用感染模型来表征NLRP3炎性小体在急性感染期间的作用。缺乏炎性小体成分NLRP3、ASC（含半胱天冬酶激活和募集结构域的凋亡斑点样蛋白）或半胱天冬酶-1的感染巨噬细胞无法加工和分泌IL-1β。发现MyD88/NF-κB信号通路对于感染巨噬细胞中促炎基因表达至关重要。缺乏NLRP3表达的C57BL/6小鼠在急性感染期间气道中无法产生IL-1β，并且这种炎症反应的缺乏导致免疫细胞激活不足和细菌清除延迟。这些发现首次报道了NLRP3炎性小体在调节炎症反应和影响急性感染期间进展中的重要性。
