Epithelium-Intrinsic NAIP/NLRC4 Inflammasome Drives Infected Enterocyte Expulsion to Restrict Salmonella Replication in the Intestinal Mucosa

被引：380

作者：

Sellin, Mikael E. ^{[1
]}

Mueller, Anna A. ^{[1
]}

Felmy, Boas ^{[1
]}

Dolowschiak, Tamas ^{[1
]}

Diard, Mederic ^{[1
]}

Tardivel, Aubry ^{[2
]}

Maslowski, Kendle M. ^{[2
,3
]}

Hardt, Wolf-Dietrich ^{[1
]}

机构：

[1] ETH, Inst Microbiol, CH-8093 Zurich, Switzerland

[2] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[3] RIKEN, Ctr Integrat Med Sci IMS, Lab Intestinal Ecosyst, Yokohama, Kanagawa 2300045, Japan

来源：

CELL HOST & MICROBE | 2014年 / 16卷 / 02期

基金：

瑞士国家科学基金会; 瑞典研究理事会;

关键词：

SEROVAR TYPHIMURIUM COLITIS; LECTIN REGIII-GAMMA; S.-TYPHIMURIUM; MOUSE MODEL; CELLS; ACTIVATION; NLRC4; CASPASE-1; HOST; MICE;

D O I：

10.1016/j.chom.2014.07.001

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in similar to 100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1 alpha/beta and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.

引用

页码：237 / 248

页数：12

共 46 条

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