Cao Yuying, He Wei, Xu Lihui, Li Wanjun, Tian Shen, Pan Fuqiang, Tang Fang, Dai Jianjun, Xue Feng
MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Bacteriology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Ningxia Hui Autonomous Region Food Testing and Research Institute, Yinchuan, China.
FASEB J. 2025 Aug 15;39(15):e70884. doi: 10.1096/fj.202500493RR.
Vibrio parahaemolyticus (V. parahaemolyticus) has been an emerging foodborne pathogen prevalent worldwide for decades, primarily due to the impact of climate change. The food safety concerns associated with V. parahaemolyticus have led to a potential risk for its control. As VopR is a V. parahaemolyticus T3SS1 effector, the function of VopR is still unclear. To address this knowledge gap, we investigated the host response to VopR during the process of V. parahaemolyticus infection. In our research, the deletion of vopR increased virulence and necrosis in host cells during infection. RNA-seq analysis revealed considerable changes in physiological processes upon V. parahaemolyticus infection. The deletion of vopR increased the transcription of proinflammatory cytokines, such as IL-6 and CXCL8, as well as the transcription of FOS and JUN family genes, indicating that VopR has a negative regulatory role in the host's proinflammatory immune response during infection. An inhibitor used to activate Erk1/2 has demonstrated that VopR suppresses host proinflammatory immune responses by stimulating MAPK-Erk1/2 activation. Coimmunoprecipitation (co-IP) and confocal microscopy confirmed that VopR interacted with host Rac1. Furthermore, when the RAC1 gene was knocked out in HeLa cells, VopR did not inhibit host cell death or decrease the transcription of CXCL8, suggesting that Rac1 is necessary for the function of VopR during V. parahaemolyticus infection. In summary, our findings indicate that VopR plays a crucial role in suppressing the proinflammatory immune response during V. parahaemolyticus infection, which can facilitate the survival of host cells during infection by V. parahaemolyticus, which contains the active T3SS1.
副溶血性弧菌（Vibrio parahaemolyticus，V. parahaemolyticus）数十年来一直是一种在全球范围内流行的新兴食源性病原体，这主要归因于气候变化的影响。与副溶血性弧菌相关的食品安全问题导致了对其进行控制的潜在风险。由于VopR是副溶血性弧菌T3SS1效应蛋白，其功能仍不清楚。为了填补这一知识空白，我们研究了在副溶血性弧菌感染过程中宿主对VopR的反应。在我们的研究中，vopR的缺失增加了感染期间宿主细胞的毒力和坏死。RNA测序分析揭示了副溶血性弧菌感染后生理过程的显著变化。vopR的缺失增加了促炎细胞因子（如IL-6和CXCL8）的转录，以及FOS和JUN家族基因的转录，表明VopR在感染期间宿主的促炎免疫反应中具有负调节作用。一种用于激活Erk1/2的抑制剂表明，VopR通过刺激MAPK-Erk1/2激活来抑制宿主促炎免疫反应。免疫共沉淀（co-IP）和共聚焦显微镜证实VopR与宿主Rac1相互作用。此外，当在HeLa细胞中敲除RAC1基因时，VopR不会抑制宿主细胞死亡或降低CXCL8的转录，这表明Rac1在副溶血性弧菌感染期间对VopR的功能是必需的。总之，我们的研究结果表明，VopR在抑制副溶血性弧菌感染期间的促炎免疫反应中起关键作用，这可以促进含有活性T3SS1的副溶血性弧菌感染期间宿主细胞的存活。
