Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
J Immunol. 2010 Jan 1;184(1):17-20. doi: 10.4049/jimmunol.0903114. Epub 2009 Nov 30.
Pathogenesis of Bacillus anthracis is associated with the production of lethal toxin (LT), which activates the murine Nalp1b/Nlrp1b inflammasome and induces caspase-1-dependent pyroptotic death in macrophages and dendritic cells. In this study, we investigated the effect of allelic variation of Nlrp1b on the outcome of LT challenge and infection by B. anthracis spores. Nlrp1b allelic variation did not alter the kinetics or pathology of end-stage disease induced by purified LT, suggesting that, in contrast to previous reports, macrophage lysis does not contribute directly to LT-mediated pathology. However, animals expressing a LT-sensitive allele of Nlrp1b showed an early inflammatory response to LT and increased resistance to infection by B. anthracis. Data presented here support a model whereby LT-mediated activation of Nlrp1b and subsequent lysis of macrophages is not a mechanism used by B. anthracis to promote virulence, but rather a protective host-mediated innate immune response.
炭疽杆菌的发病机制与致死毒素（LT）的产生有关，LT 会激活鼠 NLRP1B/NLRC4 炎性小体，并诱导巨噬细胞和树突状细胞中 caspase-1 依赖性细胞焦亡。在这项研究中，我们研究了 NLRP1B 等位基因变异对 LT 挑战和炭疽芽胞杆菌孢子感染结局的影响。NLRP1B 等位基因变异并未改变纯化 LT 诱导的终末期疾病的动力学或病理学，这表明与之前的报告相反，巨噬细胞裂解并不直接导致 LT 介导的病理学。然而，表达 LT 敏感型 NLRP1B 等位基因的动物对 LT 表现出早期炎症反应，并增加了对炭疽芽胞杆菌感染的抵抗力。本文提供的数据支持这样一种模型，即 LT 介导的 NLRP1B 激活以及随后的巨噬细胞裂解不是炭疽芽胞杆菌促进毒力的机制，而是宿主保护性的先天免疫反应。
