Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / immunology
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Adenoviridae / metabolism
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Animals
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Carrier Proteins / immunology*
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Carrier Proteins / metabolism
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Genetic Vectors / immunology
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Genetic Vectors / metabolism
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Immunity, Innate
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Integrin beta3 / immunology
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Integrin beta3 / metabolism
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Interleukin-1alpha / immunology*
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Interleukin-1alpha / metabolism
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Macrophages / cytology
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Macrophages / immunology*
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Macrophages / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NLR Family, Pyrin Domain-Containing 3 Protein
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Receptors, Interleukin-1 / immunology*
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Receptors, Interleukin-1 / metabolism
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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Toll-Like Receptor 9 / immunology*
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Toll-Like Receptor 9 / metabolism
Substances
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Carrier Proteins
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Integrin beta3
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Interleukin-1alpha
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nlrp3 protein, mouse
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Receptors, Interleukin-1
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Toll-Like Receptor 9