IL-12 deficiency transiently improves viral clearance during the late phase of respiratory tract infection with influenza A virus in mice |
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Authors: | van der Sluijs Koenraad F van Elden Leontine J R Xiao Yanling Arens Ramon Nijhuis Monique Schuurman Rob Florquin Sandrine Jansen Henk M Lutter René van der Poll Tom |
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Affiliation: | Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. kvandersluijs@amc.uva.nl |
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Abstract: | T helper 1-driven immune responses have been implicated in protective immunity against viral infections. Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a p35 and a p40 subunit that can induce differentiation of na?ve T cells towards a T helper 1-response. To determine the role of IL-12 in respiratory tract infection with influenza, p35 gene deficient (p35-/-) and normal wild type mice were intranasally infected with influenza A virus. IL-12 p35-/- mice displayed a transiently enhanced rather than an impaired viral clearance, as indicated by a 10-fold reduction in viral loads on day 8 after infection. Although interferon-gamma levels were significantly lower in the lungs of IL-12 p35-/- mice, their cellular immune responses were not altered, as reflected by similar T cell CD69 expression and influenza-specific T cell recruitment. Our data indicate that endogenous IL-12 impairs viral clearance during the late phase of influenza A virus infection in mice. |
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