Neiman-Zenevich Jana, Stuart Sarah, Abdel-Nour Mena, Girardin Stephen E, Mogridge Jeremy
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
Infect Immun. 2017 Oct 18;85(11). doi: 10.1128/IAI.00338-17. Print 2017 Nov.
Activation of the innate immune receptor NLRP1B leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. One of the signals to which NLRP1B responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. NLRP1B might therefore sense microbial infection, as intracellular pathogens such as and cause metabolic stress as a result of nutrient scavenging and host cell damage. Here we addressed whether these pathogens activate the NLRP1B inflammasome. We found that infection activated the NLRP1B inflammasome in a reconstituted fibroblast model. Activation of NLRP1B by was diminished in an NLRP1B mutant shown previously to be defective at detecting energy stress and was dependent on the expression of listeriolysin O (LLO), a protein required for vacuolar escape. Infections of either or activated NLRP1B in the RAW264.7 murine macrophage line, which expresses endogenous NLRP1B. We conclude that NLRP1B senses cellular infection by distinct invasive pathogens.
天然免疫受体NLRP1B的激活会导致炎性小体的形成，炎性小体可诱导前半胱天冬酶-1的自蛋白水解加工，最终导致炎性细胞因子的释放和细胞焦亡的发生。NLRP1B响应的信号之一是在缺乏葡萄糖的细胞或用代谢抑制剂处理的细胞中发生的代谢应激。因此，NLRP1B可能感知微生物感染，因为诸如单核细胞增生李斯特菌和肺炎衣原体等细胞内病原体由于营养清除和宿主细胞损伤而导致代谢应激。在这里，我们探讨了这些病原体是否激活NLRP1B炎性小体。我们发现在重组的成纤维细胞模型中，单核细胞增生李斯特菌感染激活了NLRP1B炎性小体。在先前显示在检测能量应激方面存在缺陷的NLRP1B突变体中，单核细胞增生李斯特菌对NLRP1B的激活减弱，并且其依赖于溶酶体溶解素O（LLO）的表达，LLO是液泡逃逸所需的一种蛋白质。单核细胞增生李斯特菌或肺炎衣原体的感染激活了表达内源性NLRP1B的RAW264.7小鼠巨噬细胞系中的NLRP1B。我们得出结论，NLRP1B可感知不同侵袭性病原体的细胞感染。
