Burdack S, Schmidt A, Knieschies E, Röllinghoff M, Beuscher H U
Institut für Klinische Mikrobiologie und Immunologie, Universität Erlangen/Nürnberg, Germany.
Med Microbiol Immunol. 1997 Mar;185(4):223-9. doi: 10.1007/s004300050034.
Previous studies have suggested that virulence of pathogenic Yersiniae is associated with a suppression of the local cytokine response. In this context, the plasmid-encoded 41-kDa Yersinia outer protein B (YopB) has been implicated with the lack of tumor necrosis factor-alpha (TNF-alpha) expression in Peyer's patches (PP), following oral infection of mice with the enteropathogenic Yersinia enterocolitica. The present study was performed to further evaluate the relationships between YopB-induced suppression of TNF-alpha and bacterial survival in host tissue. Results are presented to show the ability of purified YopB to suppress the release of TNF-alpha by macrophages, the effect of which was neutralized by monospecific anti-YopB antiserum. In mice orally infected with Y. enterocolitica, anti-YopB treatment on days 3 and 5 postinfection, significantly decreased the recovery of live bacteria from PP. This observation correlated with a strong increase in TNF-alpha expression, as determined by reverse transcription-polymerase chain reaction and measuring the levels of TNF activity in homogenates of PP. Moreover, treatment of mice with a combination of anti-YopB and anti-TNF-alpha antiserum, completely abrogated the beneficial effect of the anti-YopB antiserum. In controls, expression of other proinflammatory cytokines such as interleukin-1 remained unaffected by either treatment. Therefore, the results indicate that endogenous TNF-alpha is required for eradication of Y. enterocolitica from host tissue, and further imply that YopB significantly contributes to suppression of the local TNF-alpha response in PP.
先前的研究表明，致病性耶尔森菌的毒力与局部细胞因子反应的抑制有关。在此背景下，质粒编码的41 kDa耶尔森菌外膜蛋白B（YopB）被认为与小鼠经肠道致病性小肠结肠炎耶尔森菌口服感染后派伊尔结（PP）中肿瘤坏死因子-α（TNF-α）表达缺失有关。本研究旨在进一步评估YopB诱导的TNF-α抑制与宿主组织中细菌存活之间的关系。结果表明，纯化的YopB能够抑制巨噬细胞释放TNF-α，其作用可被单特异性抗YopB抗血清中和。在经小肠结肠炎耶尔森菌口服感染的小鼠中，感染后第3天和第5天进行抗YopB治疗，显著降低了PP中活菌的回收率。这一观察结果与TNF-α表达的强烈增加相关，这是通过逆转录-聚合酶链反应和测量PP匀浆中TNF活性水平确定的。此外，用抗YopB和抗TNF-α抗血清联合治疗小鼠，完全消除了抗YopB抗血清的有益作用。在对照组中，其他促炎细胞因子如白细胞介素-1的表达不受任何一种治疗的影响。因此，结果表明内源性TNF-α是从宿主组织中根除小肠结肠炎耶尔森菌所必需的，并且进一步表明YopB对PP中局部TNF-α反应的抑制有显著作用。
