State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Shanghai Engineering Research Center of Marine Cultured Animal Vaccines, Shanghai, 200237, China.
Microb Pathog. 2018 Oct;123:496-504. doi: 10.1016/j.micpath.2018.08.016. Epub 2018 Aug 14.
Edwardsiella piscicida is an important pathogenic bacterium that causes hemorrhagic septicemia in fish. This bacterium could activate NLRC4 and NLRP3 inflammasomes via type III secretion system (T3SS), and inhibit NLRP3 inflammasome via type VI secretion system (T6SS) effector during infection in macrophages. However, the roles of other virulence factors in regulating inflammasome activation during E. piscicida infection remain poorly understood. In this study, we focused on clarification the role of ETAE_RS10155, a thioredoxin-like protein (Trxlp), during bacterial infection in macrophages. We found that mutation of this gene barely influences the bacteria growth and infection capability. Interestingly, the inflammasome activation was reduced in Δtrxlp-infected macrophages, compared with wild-type E. piscicida did. Moreover, Trxlp mainly promotes the NLRC4, but not NLRP3 inflammasome activation during E. piscicida infection. Finally, Trxlp-mediated NLRC4 inflammasome activation is crucial for host surveillance in vivo. Taken together, our results clarify the complex and contextual role of bacterial virulence effector in modulating inflammasome activation, and offer new insights into the warfare between the fish bacterial weapons and host innate immunological surveillance.
爱德华氏菌是一种重要的致病性细菌，可引起鱼类出血性败血症。该细菌可通过 III 型分泌系统（T3SS）激活 NLRC4 和 NLRP3 炎性体，并通过 VI 型分泌系统（T6SS）效应子在巨噬细胞感染过程中抑制 NLRP3 炎性体。然而，其他毒力因子在调节爱德华氏菌感染期间炎性体激活中的作用仍知之甚少。在本研究中，我们专注于阐明一种硫氧还蛋白样蛋白（Trxlp）ETAE_RS10155 在细菌感染巨噬细胞过程中的作用。我们发现该基因的突变几乎不影响细菌的生长和感染能力。有趣的是，与野生型爱德华氏菌相比，Δtrxlp 感染的巨噬细胞中炎性体的激活减少。此外，Trxlp 主要在爱德华氏菌感染过程中促进 NLRC4 炎性体的激活，而不是 NLRP3 炎性体的激活。最后，Trxlp 介导的 NLRC4 炎性体激活对于宿主在体内的监测至关重要。总之，我们的研究结果阐明了细菌毒力效应因子在调节炎性体激活方面的复杂和背景作用，并为鱼类细菌武器和宿主固有免疫监视之间的战争提供了新的见解。
