IL-12 deficiency transiently improves viral clearance during the late phase of respiratory tract infection with influenza A virus in mice.
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 naïve 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.
van der Sluijs
Koenraad F
KF
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. kvandersluijs@amc.uva.nl
van Elden
Leontine J R
LJ
Xiao
Yanling
Y
Arens
Ramon
R
Nijhuis
Monique
M
Schuurman
Rob
R
Florquin
Sandrine
S
Jansen
Henk M
HM
Lutter
René
R
van der Poll
Tom
T
D000818:Animals; D018893:Bronchoalveolar Lavage; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000172:deficiency* / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D012141:Respiratory Tract Infections / Q000097:blood / Q000276:immunology* / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
D007136:Immunoglobulins; D018664:Interleukin-12