Beuscher H U, Rödel F, Forsberg A, Röllinghoff M
Institute for Clinical Microbiology and Immunology, University of Erlangen/Nürnberg, Germany.
Infect Immun. 1995 Apr;63(4):1270-7. doi: 10.1128/iai.63.4.1270-1277.1995.
The ability of the enteropathogenic Yersinia enterocolitica to survive and proliferate in host tissue depends on a 70-kb plasmid known to encode a number of released Yersinia outer proteins that act as virulence factors by inducing cytotoxicity and inhibiting phagocytosis. This study demonstrates that one of the Yersinia outer proteins, the 41-kDa YopB, suppresses the production of tumor necrosis factor alpha (TNF-alpha), a macrophage-derived cytokine with central roles in the regulation of immune and inflammatory responses to infection. This conclusion is based on several lines of evidence. First, in macrophage cultures, suppression of TNF-alpha mRNA expression was induced by culture supernatant (CS+) of plasmid-bearing yersiniae, the effect which was blocked by anti-YopB antiserum. Second, suppression of TNF-alpha production, but not of interleukin-1 (IL-1) and IL-6, was induced by purified YopB. Third, in Yersinia-infected mice, no increase in TNF-alpha mRNA expression was observed in Peyer's patches, the primary site of bacterial invasion, compared with IL-1 (alpha and beta) mRNA. Finally, administration of anti-YopB antiserum to mice prior to infection with Y. enterocolitica increased TNF activity levels in Peyer's patches and coincided with a reduction in bacterial growth. The results thus provide direct evidence for a secreted eubacterial virulence factor that mediates selective suppression of TNF-alpha production. Although suppression of this single cytokine response is probably not sufficient to facilitate survival of the infecting organisms, the results suggest that suppression of TNF-alpha production by YopB significantly contributes to the evasion of Y. enterocolitica from antibacterial host defense.
肠道致病性小肠结肠炎耶尔森氏菌在宿主组织中存活和增殖的能力取决于一个70 kb的质粒，已知该质粒编码一些释放的耶尔森氏菌外膜蛋白，这些蛋白通过诱导细胞毒性和抑制吞噬作用而作为毒力因子发挥作用。本研究表明，耶尔森氏菌外膜蛋白之一、41 kDa的YopB可抑制肿瘤坏死因子α（TNF-α）的产生，TNF-α是一种巨噬细胞衍生的细胞因子，在调节对感染的免疫和炎症反应中起核心作用。这一结论基于多条证据。首先，在巨噬细胞培养物中，携带质粒的耶尔森氏菌的培养上清液（CS+）可诱导TNF-α mRNA表达的抑制，抗YopB抗血清可阻断该效应。其次，纯化的YopB可诱导TNF-α产生的抑制，但不影响白细胞介素-1（IL-1）和IL-6的产生。第三，在感染耶尔森氏菌的小鼠中，与IL-1（α和β）mRNA相比，在细菌入侵的主要部位派伊尔结中未观察到TNF-α mRNA表达增加。最后，在感染小肠结肠炎耶尔森氏菌之前给小鼠注射抗YopB抗血清可提高派伊尔结中的TNF活性水平，并与细菌生长的减少相一致。因此，这些结果为一种分泌型真细菌毒力因子介导TNF-α产生的选择性抑制提供了直接证据。虽然对这单一细胞因子反应的抑制可能不足以促进感染微生物的存活，但结果表明YopB对TNF-α产生的抑制显著有助于小肠结肠炎耶尔森氏菌逃避宿主的抗菌防御。
