Superoxide Production by NADPH Oxidase Intensifies Macrophage Antiviral Responses during Diabetogenic Coxsackievirus Infection.

Autor:	Burg AR; Comprehensive Diabetes Center, Department of Microbiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294-2182., Das S; Comprehensive Diabetes Center, Department of Microbiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294-2182., Padgett LE; Comprehensive Diabetes Center, Department of Microbiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294-2182., Koenig ZE; Comprehensive Diabetes Center, Department of Microbiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294-2182., Tse HM; Comprehensive Diabetes Center, Department of Microbiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294-2182 htse@uab.edu.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Jan 01; Vol. 200 (1), pp. 61-70. Date of Electronic Publication: 2017 Nov 20.
DOI:	10.4049/jimmunol.1700478
Abstrakt:	Coxsackievirus B infections are suspected environmental triggers of type 1 diabetes (T1D) and macrophage antiviral responses may provide a link to virus-induced T1D. We previously demonstrated an important role for NADPH oxidase (NOX)-derived superoxide production during T1D pathogenesis, as NOX-deficient NOD mice (NOD. Ncf1 m1J ) were protected against T1D due, in part, to impaired proinflammatory TLR signaling in NOD. Ncf1 m1J macrophages. Therefore, we hypothesized that loss of NOX-derived superoxide would dampen diabetogenic antiviral macrophage responses and protect from virus-induced diabetes. Upon infection with a suspected diabetogenic virus, Coxsackievirus B3 (CB3), NOD. Ncf1 m1J mice remained resistant to virus-induced autoimmune diabetes. A concomitant decrease in circulating inflammatory chemokines, blunted antiviral gene signature within the pancreas, and reduced proinflammatory M1 macrophage responses were observed. Importantly, exogenous superoxide addition to CB3-infected NOD. Ncf1 m1J bone marrow-derived macrophages rescued the inflammatory antiviral M1 macrophage response, revealing reduction-oxidation-dependent mechanisms of signal transducer and activator of transcription 1 signaling and dsRNA viral sensors in macrophages. We report that superoxide production following CB3 infection may exacerbate pancreatic β cell destruction in T1D by influencing proinflammatory M1 macrophage responses, and mechanistically linking oxidative stress, inflammation, and diabetogenic virus infections. (Copyright © 2017 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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