Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo.
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.
Di Paolo
Nelson C
NC
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Miao
Edward A
EA
Iwakura
Yoichiro
Y
Murali-Krishna
Kaja
K
Aderem
Alan
A
Flavell
Richard A
RA
Papayannopoulou
Thalia
T
Shayakhmetov
Dmitry M
DM
D000256:Adenoviridae / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D039661:Integrin beta3 / Q000276:immunology / Q000378:metabolism; D053582:Interleukin-1alpha / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017472:Receptors, Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism
D002352:Carrier Proteins; D039661:Integrin beta3; D053582:Interleukin-1alpha; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017472:Receptors, Interleukin-1; D051217:Toll-Like Receptor 9