TLR2 and TLR4 mediate the TNFα response to Vibrio vulnificus biotype 1.
TLR2 and TLR4 mediate the TNFα response to Vibrio vulnificus biotype 1.
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TLR2 和 TLR4 介导对创伤弧菌生物型 1 的 TNFα 反应。
DOI：
10.1111/2049-632x.12154
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发表时间：
2014
影响因子：
3.3
通讯作者：
Drapp,RebeccaL
中科院分区：
文献类型：
--
作者：
Stamm,LolaV;Drapp,RebeccaL
创伤弧菌（Vibrio vulnificus, Vv）是一种致病菌，可引起危及生命的感染。大多数致命病例是由于细胞因子，特别是TNFα的失调引起的脓毒性休克，TNFα在感染的结果中起着关键作用。本研究的目的是利用TLR2、TLR4和TLR2/TLR4缺陷小鼠，研究Toll样受体（TLR）介导的TNFα对四种vvbiotype 1菌株的应答。采用福尔马林灭活vv （fVv）作为刺激剂，对野生型（WT）和TLR敲除（KO）小鼠的血液、脾细胞和库普弗细胞（KC）进行体外实验。所有fVvbiotype 1菌株均能诱导WT小鼠血液和细胞产生较强的TNFα，并依赖于TLR2和TLR4。OxPAPC是TLR2和TLR4信号的抑制剂，有效地减弱了TLR介导的TNFα对fVv的反应。此外，TLR2 KO和TLR2/TLR4 KO小鼠比WT小鼠更能抵抗vvatcc 27562致死感染，这可能是由于TNFα反应的衰减。这些数据表明，有可能设计出专门针对有害的TLR介导的TNFα反应的策略，作为抗生素治疗严重感染的辅助手段。
Vibrio vulnificus(Vv) is a pathogenic bacterium that can cause life threatening infections in humans. Most fatal cases are due to septic shock that results from dysregulation of cytokines, particularly TNFα, which plays a critical role in the outcome ofVvinfection. The goal of this study was to investigate the Toll like receptor (TLR) mediated TNFα response to fourVvbiotype 1 strains using mice deficient for TLR2, TLR4, and TLR2/TLR4.Ex vivoassays were performed with blood, splenocytes, and Kupffer cells (KC) from wild type (WT) and TLR knockout (KO) mice using formalin inactivatedVv(fVv) as stimulant. All fVvbiotype 1 strains elicited strong TNFα production by WT mouse blood and cells, which was TLR2 and TLR4 dependent. OxPAPC, an inhibitor of TLR2 and TLR4 signaling, effectively blunted the TLR mediated TNFα response to fVv. Furthermore, TLR2 KO and TLR2/TLR4 KO mice were more resistant to lethal infection withVvATCC 27562 than WT mice, perhaps due to attenuation of the TNFα response. These data suggest that it may be possible to devise strategies to specifically target the harmful TLR mediated TNFα response as an adjunct to antibiotic treatment of severeVvinfection.