NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense.
NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense.
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肠道吞噬细胞运输口服抗原并促进免疫耐受，但它们在先天免疫反应中的作用仍不清楚。在此我们报道肠道吞噬细胞对Toll样受体配体或共生菌无反应，但组成性表达前白细胞介素 - 1β（proIL - 1β）。在感染致病性沙门氏菌或假单胞菌时，肠道吞噬细胞通过NLRC4炎症小体产生成熟的白细胞介素 - 1β，但不产生肿瘤坏死因子或白细胞介素 - 6。Balb/c背景下NLRC4或白细胞介素 - 1受体缺陷的小鼠对经口感染沙门氏菌高度易感，但对腹腔感染不敏感。在致死率增加之前，内皮黏附分子表达受损、中性粒细胞募集减少以及肠道病原体清除不佳。因此，肠道吞噬细胞通过NLRC4依赖的白细胞介素 - 1β产生代表了一种区分病原菌和共生菌的特异性反应，并有助于肠道的宿主防御。
Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we report that intestinal phagocytes are anergic to Toll-like receptor ligands or commensals, but constitutively express pro-interleukin-1β (proIL-1β). Upon infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produce mature IL-1β through the NLRC4 inflammasome, but not tumor necrosis factor or IL-6. Mice deficient in NLRC4 or IL-1 receptor on a Balb/c background were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. Increased lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment, and poor intestinal pathogen clearance. Thus, NLRC4-dependent IL-1β production by intestinal phagocytes represents a specific response discriminating pathogenic from commensal bacteria and contributes to host defense in the intestine.
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影响因子：
64.8
作者：
Brandl, Katharina;Plitas, George;Mihu, Coralia N.;Ubeda, Carles;Jia, Ting;Fleisher, Martin;Schnabl, Bernd;DeMatteo, Ronald P.;Pamer, Eric G.
通讯作者：
Pamer, Eric G.
影响因子：
8.7
作者：
Manicassamy S;Pulendran B
通讯作者：
Pulendran B
DOI：
10.1073/pnas.1016814108
发表时间：
2010-12-14
影响因子：
11.1
作者：
Hu, Bo;Elinav, Eran;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
5.4
作者：
Franchi, Luigi;Stoolman, Joshua;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
30.5
作者：
Franchi, Luigi;Amer, Amal;Nunez, Gabriel
通讯作者：
Nunez, Gabriel