Antiviral Antibodies Target Adenovirus to Phagolysosomes and Amplify the Innate Immune Response
| Autor: | Sharon A. Clark, Akosua Vilaysane, Daniel A. Muruve, H. Christopher Meijndert, Virginie Pétrilli, Anne K. Zaiss, Pina Colarusso, Matthew J. Cotter, Jürg Tschopp, Robin M. Yates |
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| Rok vydání: | 2009 |
| Předmět: |
Adenoviridae Infections
viruses media_common.quotation_subject Immunology chemical and pharmacologic phenomena Biology Antibodies Viral medicine.disease_cause Adenoviridae Viral vector Mice Phagocytosis Phagosomes medicine Animals Immunology and Allergy Adenovirus infection Internalization Phagosome media_common Innate immune system Macrophages biochemical phenomena metabolism and nutrition Acquired immune system medicine.disease Virology Immunity Innate Up-Regulation biology.protein Antibody |
| Zdroj: | The Journal of Immunology. 182:7058-7068 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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-κB-dependent genes, type I IFNs, and caspase-dependent IL-1β maturation. Immune serum amplified TLR9-independent type I IFN expression and enhanced NLRP3-dependent IL-1β 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. |
| Databáze: | OpenAIRE |
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