Vibrio vulnificus Hemolysin Induces TNF-α Independent ROS Production by Primary Murine Macrophages [post]

Yong-Liang Lou, Dan-Li Xie, Xian-Hui Huang, Meng-Meng Zheng, Ting Zhang, Jiru Xu
2021 unpublished
BackgroundVibrio vulnificus (V. vulnificus) is a gram-negative opportunistic pathogen that causes lethal infections in humans. Vibrio vulnificus hemolysin (VVH) is a key virulence factor that exhibits strong hemolytic and cytolytic activities and contributes to the pathogen's invasion, vasodilatation, and septic shock. Most of the studies so far have focused on VVH's cytolytic activity against cell lines derived from host cells. However, the cytolytic activity of VVH on primary macrophages is
more » ... ry macrophages is still unclear. In addition, although it is known that VVH induces host cell apoptosis via triggering ROS production, the impact of VVH on host immune response has not been fully understood. This study aimed to investigate the role of VVH-induced TNF-α expression and ROS production in the absence of apoptosis of murine primary macrophages and related signaling pathways using FACS, DCFH-DA, real-time PCR, and western blotting. ResultsThe results showed that murine primary macrophages from different organs displayed differential sensitivities towards VVH-induced cell death. Liver Kupffer cells, splenic macrophages, and BMMfs were more sensitive to VVH-induced cytotoxicity, while alveolar macrophages, lung interstitial macrophages, and lung neutrophils were resistant to VVH-induced cell death. Besides, we found that a low dose of VVH, which did not induce apoptosis in murine primary macrophages, could induce apoptosis independent TNF-α expression and ROS generation. Such ROS production in macrophages could be further blocked by inhibiting p38-MAPKs or NFκB activation but was not affected by knockout of TNF-α. ConclusionsVVH produced cytotoxicity in macrophages, an apoptosis-independent TNF-α expression, and ROS production, which provides insight into the mechanism underlying the crosstalk between VVH-induced inflammation and oxidative stress.
doi:10.21203/rs.3.rs-147505/v1 fatcat:sws2ererhjdz3l6jdtptomtexu