Virus Binding to a Plasma Membrane Receptor Triggers Interleukin-1α-Mediated Proinflammatory Macrophage Response In Vivo

被引：165

作者：

Di Paolo, Nelson C. ^{[1
]}

Miao, Edward A.

Iwakura, Yoichiro ^{[5
,6
]}

Murali-Krishna, Kaja ^{[2
]}

Aderem, Alan ^{[4
]}

Flavell, Richard A. ^{[7
,8
]}

Papayannopoulou, Thalia ^{[3
]}

Shayakhmetov, Dmitry M. ^{[1
]}

机构：

[1] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA

[2] Univ Washington, Dept Immunol, Seattle, WA 98195 USA

[3] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA

[4] Inst Syst Biol, Seattle, WA 98103 USA

[5] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan

[6] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan

[7] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA

[8] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

来源：

IMMUNITY | 2009年 / 31卷 / 01期

关键词：

VASCULAR ENDOTHELIAL-CELLS; INNATE IMMUNE-RESPONSE; ADENOVIRAL VECTORS; MICE DEFICIENT; EPITHELIAL-CELLS; GENE-EXPRESSION; RIG-I; ACTIVATION; INFECTION; TOXICITY;

D O I：

10.1016/j.immuni.2009.04.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The recognition of viral components by host pattern-recognition receptors triggers the induction of the antiviral innate immune response. Toll-like receptor 9 (TLR9) and NLRP3 inflammasome were shown to be the principal specific sensors of viral double-stranded DNA. Here we present evidence that macrophages in vivo activated an innate immune response to a double-stranded DNA virus, adenovirus (Ad), independently of TLR9 or NLRP3 inflammasome. In response to Ad, macrophage-derived IL-1 alpha triggered IL-1RI-dependent production of a defined set of proinflammatory cytokines and chemokines. The IL-1 alpha-mediated response required a selective interaction of virus arginine-glycine-aspartic acid (RGD) motifs with macrophage beta(3) integrins. Thus, these data identify IL-1 alpha-IL-1RI as a key pathway allowing for the activation of proinflammatory responses to the virus, independently of its genomic nucleic acid recognition.

引用

页码：110 / 121

页数：12

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