The University of Texas Health Science Center at San Antonio, Department of Microbiology and Immunology, San Antonio, Texas, USA.
Infect Immun. 2012 Jan;80(1):289-97. doi: 10.1128/IAI.05742-11. Epub 2011 Nov 14.
Yersinia enterocolitica is a food-borne pathogen that preferentially infects the Peyer's patches and mesenteric lymph nodes, causing an acute inflammatory reaction. Even though Y. enterocolitica induces a robust inflammatory response during infection, the bacterium has evolved a number of virulence factors to limit the extent of this response. We previously demonstrated that interleukin-1α (IL-1α) was critical for the induction of gut inflammation characteristic of Y. enterocolitica infection. More recently, the known actions of IL-1α are becoming more complex because IL-1α can function both as a proinflammatory cytokine and as a nuclear factor. In this study, we tested the ability of Y. enterocolitica to modulate intracellular IL-1α-dependent IL-8 production in epithelial cells. Nuclear translocation of pre-IL-1α protein and IL-1α-dependent secretion of IL-8 into the culture supernatant were increased during infection with a strain lacking the 70-kDa virulence plasmid compared to the case during infection with the wild type, suggesting that Yersinia outer proteins (Yops) might be involved in modulating intracellular IL-1α signaling. Infection of HeLa cells with a strain lacking the yopP gene resulted in increased nuclear translocation of pre-IL-1α and IL-1α-dependent secretion of IL-8 similar to what is observed with bacteria lacking the virulence plasmid. YopP is a protein acetylase that inhibits mitogen-activated protein kinase (MAP kinase)- and NF-κB-dependent signal transduction pathways. Nuclear translocation of pre-IL-1α and IL-1α-dependent secretion of IL-8 in response to Yersinia enterocolitica infection were dependent on extracellular signal-regulated kinase (ERK) and p38 MAP kinase signaling but independent of NF-κB. These data suggest that Y. enterocolitica inhibits intracellular pre-IL-1α signaling and subsequent proinflammatory responses through inhibition of MAP kinase pathways.
耶尔森氏菌是一种食源性病原体，优先感染派尔集合淋巴结和肠系膜淋巴结，引起急性炎症反应。尽管耶尔森氏菌在感染过程中引起强烈的炎症反应，但该细菌已进化出多种毒力因子来限制这种反应的程度。我们之前证明白细胞介素-1α（IL-1α）对于诱导耶尔森氏菌感染特征性的肠道炎症至关重要。最近，IL-1α的已知作用变得更加复杂，因为 IL-1α既可以作为促炎细胞因子，也可以作为核因子。在这项研究中，我们测试了耶尔森氏菌在感染上皮细胞时调节细胞内 IL-1α依赖性 IL-8 产生的能力。与野生型感染相比，缺乏 70kDa 毒力质粒的菌株感染时，前 IL-1α 蛋白的核易位和 IL-1α 依赖性 IL-8 分泌增加，表明耶尔森氏菌外蛋白（Yops）可能参与调节细胞内 IL-1α 信号。用缺乏 yopP 基因的菌株感染 HeLa 细胞导致前 IL-1α 的核易位和 IL-1α 依赖性 IL-8 分泌增加，类似于缺乏毒力质粒的细菌。YopP 是一种蛋白乙酰酶，可抑制丝裂原活化蛋白激酶（MAPK）和 NF-κB 依赖性信号转导途径。对耶尔森氏菌感染的反应中，前 IL-1α 的核易位和 IL-1α 依赖性 IL-8 分泌依赖于细胞外信号调节激酶（ERK）和 p38 MAPK 信号，但独立于 NF-κB。这些数据表明，耶尔森氏菌通过抑制 MAPK 途径抑制细胞内前 IL-1α 信号和随后的促炎反应。
