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
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
收藏
页码:110 / 121
页数:12
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