Protective role of interleukin-6 during Yersinia enterocolitica infection is mediated through the modulation of inflammatory cyokines
Protective role of interleukin-6 during Yersinia enterocolitica infection is mediated through the modulation of inflammatory cyokines
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DOI：
10.1128/iai.72.6.3561-3570.2004
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Miller, VL
中科院分区：
文献类型：
--
作者：
Dube, PH;Handley, SA;Miller, VL
小肠结肠炎耶尔森氏菌是一种革兰氏阴性肠道病原体，可导致许多胃肠道疾病。小肠结肠炎耶尔森菌感染的一个显著的病理特征是炎症。最近，我们证实了白介素1α(IL-1α)在小肠结肠炎耶尔森菌感染的肠道炎症反应中的作用。IL-1水平直接影响的细胞因子是IL-6。先前的一篇报道表明，IL-6在小肠结肠炎耶尔森菌感染过程中发挥抗炎作用，而在其他系统中，IL-6已被证明是促炎的。因此，我们进一步研究了IL-6和炎性细胞因子在控制IL-6(-/-)小鼠小肠结肠炎耶尔森菌感染中的作用。小肠结肠炎耶尔森菌在IL-6(-/-)小鼠中的毒力更强(将致死量降低了60倍)，并比野生型小鼠更快地在全身组织中定植，达到了更高的水平。IL-6在小肠结肠炎耶尔森菌感染中的作用之一可能是下调炎症反应。IL-6(-/-)小鼠有更强大的T(H)1 T细胞反应，以及高炎症病理。这些表型似乎是由于IL-6(-/-)小鼠的肿瘤坏死因子α、单核细胞趋化蛋白1、IL-10、转化生长因子β1和伽马干扰素的错误调节所致。这些数据为进一步了解参与调节炎症反应和控制细菌感染的复杂细胞因子信号通路提供了进一步的见解。
Yersinia enterocolitica is a gram-negative enteric pathogen responsible for a number of gastrointestinal disorders. A striking feature of the pathology of a Y. enterocolitica infection is inflammation. Recently, we demonstrated a role for interleukin-1alpha (IL-1alpha) in the establishment of intestinal inflammation in response to a Y. enterocolitica infection. A cytokine directly affected by IL-1 levels is IL-6. A previous report suggested that IL-6 plays an anti-inflammatory role during Y. enterocolitica infection, and in other systems IL-6 has been shown to be proinflammatory. Therefore, a closer examination of the roles of IL-6 and inflammatory cytokines in the control of Y. enterocolitica infection in IL-6(-/-) mice was undertaken. Y. enterocolitica organisms were more virulent in the IL-6(-/-) mice (60-fold decreased 50% lethal dose) and colonized systemic tissues more rapidly and to a higher level than in the wild-type mice. One role of IL-6 during a Y. enterocolitica infection may be the downmodulation of the inflammatory response. The IL-6(-/-) mice have a more robust T(H)1 T-cell response, as well as hyperinflammatory pathologies. These phenotypes appear to be due to the misregulation of tumor necrosis factor alpha, monocyte chemotactic protein 1, IL-10, transforming growth factor beta1, and gamma interferon in the IL-6(-/-) mouse. These data provide further insight into the intricate cytokine signaling pathways involved in the regulation of inflammatory responses and the control of bacterial infections.