Department of Molecular Bacteriology and Immunology, Graduate School of Medicine, University of the Ryukyus, Nishiharacho, Okinawa, Japan.
J Immunol. 2010 Dec 1;185(11):7077-84. doi: 10.4049/jimmunol.1002165. Epub 2010 Oct 29.
Aeromonas spp. are Gram-negative bacteria that cause serious infectious disease in humans. Such bacteria have been shown to induce apoptosis in infected macrophages, yet the host responses triggered by macrophage death are largely unknown. In this study, we demonstrate that the infection of mouse bone marrow-derived macrophages with Aeromonas veronii biotype sobria triggers activation of caspase-1 with the ensuing release of IL-1β and pyroptosis. Caspase-1 activation in response to A. veronii infection requires the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain and both the NLRP3 and NLRC4 inflammasomes. Furthermore, caspase-1 activation requires aerolysin and a functional type III secretion system in A. veronii. Aerolysin-inducing caspase-1 activation is mediated through the NLRP3 inflammasome, with aerolysin-mediated cell death being largely dependent on the NLRP3 inflammasome. In contrast, the type III secretion system activates both the NLRP3 and NLRC4 inflammasomes. Inflammasome-mediated caspase-1 activation is also involved in host defenses against systemic A. veronii infection in mice. Our results indicated that multiple factors from both the bacteria and the host play a role in eliciting caspase-1 activation during A. veronii infection.
气单胞菌属是革兰氏阴性细菌，可导致人类严重的传染病。这些细菌已被证明可诱导感染的巨噬细胞发生细胞凋亡，但宿主对巨噬细胞死亡所引发的反应在很大程度上尚不清楚。在这项研究中，我们证明了温和气单胞菌生物型感染小鼠骨髓来源的巨噬细胞会触发半胱天冬酶-1 的激活，进而导致白细胞介素-1β和细胞焦亡的释放。巨噬细胞对气单胞菌感染的半胱天冬酶-1 激活需要衔接蛋白含有半胱天冬酶募集结构域的凋亡相关斑点样蛋白，以及 NLRP3 和 NLRC4 炎性小体。此外， caspase-1 的激活需要气溶素和 A. veronii 中的功能性 III 型分泌系统。气溶素诱导 caspase-1 激活是通过 NLRP3 炎性小体介导的，气溶素介导的细胞死亡在很大程度上依赖于 NLRP3 炎性小体。相比之下，III 型分泌系统激活了 NLRP3 和 NLRC4 炎性小体。炎性小体介导的半胱天冬酶-1 激活也参与了宿主对系统性气单胞菌感染的防御。我们的结果表明，在气单胞菌感染过程中，细菌和宿主的多种因素都参与了 caspase-1 的激活。
