Stamm Lola V
Department of Epidemiology, The University of North Carolina at Chapel Hill, 27599-7435, USA.
FEMS Immunol Med Microbiol. 2010 Apr;58(3):336-43. doi: 10.1111/j.1574-695X.2009.00643.x. Epub 2009 Dec 10.
The incidence of infection with Vibrio vulnificus is increasing due to changing ecologic and demographic factors. Most fatal cases are caused by septic shock that results from dysregulation of proinflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha), presumably due to interaction of V. vulnificus components with Toll-like receptors (TLRs). The goal of this study was to investigate the role of TLR4 in the host response to V. vulnificus. Results obtained using V. vulnificus type strain ATCC 27562 showed that (1) TLR4 signaling is myeloid differentiation factor 88 dependent and plays a key role in TNFalpha production by mouse blood and splenocytes stimulated ex vivo with inactivated V. vulnificus cells, (2) TLR4 signaling is deleterious in a mouse model of V. vulnificus infection, (3) signaling by TLR(s), exclusive of TLR4, is needed to eradicate infection, and (4) the TLR-mediated TNFalpha response plays a critical role in determining the outcome of infection. These results suggest that blockade of the harmful TLR4-mediated inflammatory response could be a useful adjunct to antibiotics for treatment of severe V. vulnificus infection.
由于生态和人口因素的变化，创伤弧菌感染的发病率正在上升。大多数致命病例是由脓毒性休克引起的，脓毒性休克是由促炎细胞因子（如肿瘤坏死因子-α （TNFα））失调所致，这可能是由于创伤弧菌成分与Toll样受体（TLR）相互作用的结果。本研究的目的是调查TLR4在宿主对创伤弧菌反应中的作用。使用创伤弧菌标准菌株ATCC 27562获得的结果表明：（1）TLR4信号传导依赖于髓样分化因子88，并且在体外被灭活的创伤弧菌细胞刺激的小鼠血液和脾细胞产生TNFα中起关键作用；（2）TLR4信号传导在创伤弧菌感染的小鼠模型中是有害的；（3）根除感染需要TLR（不包括TLR4）的信号传导；（4）TLR介导的TNFα反应在决定感染结果中起关键作用。这些结果表明，阻断有害的TLR4介导的炎症反应可能是治疗严重创伤弧菌感染的抗生素的有用辅助手段。
