Antiviral antibodies target adenovirus to phagolysosomes and amplify the innate immune response.

Details

Serval ID
serval:BIB_9CC4FD7200E9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antiviral antibodies target adenovirus to phagolysosomes and amplify the innate immune response.
Journal
Journal of immunology
Author(s)
Zaiss A.K., Vilaysane A., Cotter M.J., Clark S.A., Meijndert H.C., Colarusso P., Yates R.M., Petrilli V., Tschopp J., Muruve D.A.
ISSN
1550-6606[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
182
Number
11
Pages
7058-7068
Language
english
Abstract
Adenovirus is a nonenveloped dsDNA virus that activates intracellular innate immune pathways. In vivo, adenovirus-immunized mice displayed an enhanced innate immune response and diminished virus-mediated gene delivery following challenge with the adenovirus vector AdLacZ suggesting that antiviral Abs modulate viral interactions with innate immune cells. Under naive serum conditions in vitro, adenovirus binding and internalization in macrophages and the subsequent activation of innate immune mechanisms were inefficient. In contrast to the neutralizing effect observed in nonhematopoietic cells, adenovirus infection in the presence of antiviral Abs significantly increased FcR-dependent viral internalization in macrophages. In direct correlation with the increased viral internalization, antiviral Abs amplified the innate immune response to adenovirus as determined by the expression of NF-kappaB-dependent genes, type I IFNs, and caspase-dependent IL-1beta maturation. Immune serum amplified TLR9-independent type I IFN expression and enhanced NLRP3-dependent IL-1beta maturation in response to adenovirus, confirming that antiviral Abs specifically amplify intracellular innate pathways. In the presence of Abs, confocal microscopy demonstrated increased targeting of adenovirus to LAMP1-positive phagolysosomes in macrophages but not epithelial cells. These data show that antiviral Abs subvert natural viral tropism and target the adenovirus to phagolysosomes and the intracellular innate immune system in macrophages. Furthermore, these results illustrate a cross-talk where the adaptive immune system positively regulates the innate immune system and the antiviral state.
Keywords
Adenoviridae/immunology, Adenoviridae Infections/immunology, Animals, Antibodies, Viral/immunology, Immunity, Innate/immunology, Macrophages/immunology, Macrophages/virology, Mice, Phagocytosis, Phagosomes/immunology, Up-Regulation/genetics, Up-Regulation/immunology
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2009 14:51
Last modification date
20/08/2019 15:03
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