白细胞介素-27/白细胞介素-27 受体信号转导在艰难梭菌诱导的结肠炎中提供保护。

IL-27/IL-27 Receptor Signaling Provides Protection in Clostridium difficile-Induced Colitis.

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, China.

出版信息

J Infect Dis. 2018 Jan 4;217(2):198-207. doi: 10.1093/infdis/jix581.

DOI:10.1093/infdis/jix581

PMID:29140433

Abstract

BACKGROUND

Clostridium difficile is a leading cause of nosocomial infection. The role of cytokine interleukin-27 (IL-27) in the immunopathology of C. difficile infection (CDI) remains unknown.

METHODS

The production of IL-27 was determined in human and murine CDI. Furthermore, wild-type (WT) and IL-27 receptor-deficient (WSX-1-/-) mice were treated with an antibiotic mixture and infected with C. difficile to investigate the effects of IL-27 on host response to CDI.

RESULTS

IL-27 production was elevated during CDI in humans and mice. Infected WSX-1-/- mice experienced increased weight loss, enhanced colonic histology damage, less C. difficile clearance, and decreased survival compared to WT controls during CDI. IL-27 administration reduced CDI-associated mortality and tissue pathology with improved C. difficile clearance in WT mice after C. difficile challenge. Mechanistically, IL-27-mediated host defense against CDI was associated with downregulation of IL-17A and IL-23, but upregulation of IL-10 and interferon-gamma during CDI.

CONCLUSIONS

Our data suggest a previously unrecognized role for IL-27 in the pathogenesis of CDI, potentially providing new insight for IL-27-mediated protection against C. difficile-induced pathology.

摘要

背景

艰难梭菌是医院感染的主要原因。细胞因子白细胞介素-27（IL-27）在艰难梭菌感染（CDI）的免疫病理学中的作用尚不清楚。

方法

测定了人源和鼠源 CDI 中 IL-27 的产生。此外，用抗生素混合物治疗野生型（WT）和 IL-27 受体缺陷（WSX-1-/-）小鼠，并感染艰难梭菌，以研究 IL-27 对宿主对 CDI 反应的影响。

结果

在人类和小鼠的 CDI 中，IL-27 的产生增加。与 WT 对照组相比，感染 WSX-1-/-小鼠在 CDI 期间经历了体重减轻增加、结肠组织学损伤加重、艰难梭菌清除减少和存活率降低。在艰难梭菌挑战后，IL-27 给药可降低 WT 小鼠 CDI 相关死亡率和组织病理学，并改善艰难梭菌清除。在机制上，IL-27 介导的宿主防御 CDI 与 IL-17A 和 IL-23 的下调有关，但与 CDI 期间的 IL-10 和干扰素-γ的上调有关。