Interleukin-22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice
Interleukin-22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice
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DOI：
10.1111/imm.12414
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发表时间：
2015-04-01
期刊：
影响因子：
6.4
通讯作者：
Huffnagle, Gary B.
中科院分区：
文献类型：
--
作者：
Akha, Amir A. Sadighi;McDermott, Andrew J.;Huffnagle, Gary B.
我们先前的工作已经显示了IL 22的显著上调和信号转导子和转录激活子3（STAT 3）的磷酸化增加作为小鼠中对艰难梭菌感染的粘膜炎症反应的一部分。其他研究表明，粘膜表面的STAT 3磷酸化包括白细胞介素-22（IL-22）和CD 160介导的成分。本研究旨在确定IL-22和/或CD 160在艰难梭菌感染的粘膜应答中的潜在作用。与未接受任一抗体的艰难梭菌感染小鼠相比，用抗IL-22、抗CD 160或两者的组合治疗的艰难梭菌感染小鼠显示出显著降低的STAT 3磷酸化。此外，用抗IL-22/CD 160治疗的艰难梭菌感染的小鼠诱导了更少的基因组，并且水平显著低于未治疗的艰难梭菌感染的小鼠。受影响的基因包括促炎趋化因子和细胞因子以及抗菌肽。此外，组织病理学和流式细胞术评估均显示用抗IL-22/CD 160处理的艰难梭菌感染小鼠中嗜中性粒细胞的流入显著减少。这些数据表明，IL-22和CD 160共同负责艰难梭菌感染中结肠STAT 3磷酸化的显著部分。他们还强调了IL-22和CD 160在介导这种感染中宿主粘膜反应的促炎和促存活方面的累加效应。
Our previous work has shown the significant up-regulation of Il22 and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) as part of the mucosal inflammatory response to Clostridium difficile infection in mice. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes interleukin-22 (IL-22) and CD160-mediated components. The current study sought to determine the potential role(s) of IL-22 and/or CD160 in the mucosal response to C.difficile infection. Clostridium difficile-infected mice treated with anti-IL-22, anti-CD160 or a combination of the two showed significantly reduced STAT3 phosphorylation in comparison to C.difficile-infected mice that had not received either antibody. In addition, C.difficile-infected mice treated with anti-IL-22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C.difficile-infected mice. The affected genes included pro-inflammatory chemokines and cytokines, and anti-microbial peptides. Furthermore, histopathological and flow cytometric assessments both showed a significantly reduced influx of neutrophils in C.difficile-infected mice treated with anti-IL-22/CD160. These data demonstrate that IL-22 and CD160 are together responsible for a significant fraction of the colonic STAT3 phosphorylation in C.difficile infection. They also underscore the additive effects of IL-22 and CD160 in mediating both the pro-inflammatory and pro-survival aspects of the host mucosal response in this infection.