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© Michaela Muller-Trutwin
HIV
Publication : Journal of immunology (Baltimore, Md. : 1950)

Negative impact of IFN-γ on early host immune responses to retroviral infection

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 20 Jul 2012

Duley AK, Ploquin MJ, Eksmond U, Ammann CG, Messer RJ, Myers L, Hasenkrug KJ, Kassiotis G

Link to Pubmed [PMID] – 22821964

J. Immunol. 2012 Sep;189(5):2521-9

The immune system is tasked with defending against a myriad of microbial infections, and its response to a given infectious microbe may be strongly influenced by coinfection with another microbe. It was shown that infection of mice with lactate dehydrogenase-elevating virus (LDV) impairs early adaptive immune responses to Friend virus (FV) coinfection. To investigate the mechanism of this impairment, we examined LDV-induced innate immune responses and found LDV-specific induction of IFN-α and IFN-γ. LDV-induced IFN-α had little effect on FV infection or immune responses, but unexpectedly, LDV-induced IFN-γ production dampened Th1 adaptive immune responses and enhanced FV infection. Two distinct effects were identified. First, LDV-induced IFN-γ signaling indirectly modulated FV-specific CD8+ T cell responses. Second, intrinsic IFN-γ signaling in B cells promoted polyclonal B cell activation and enhanced early FV infection, despite promotion of germinal center formation and neutralizing Ab production. Results from this model reveal that IFN-γ production can have detrimental effects on early adaptive immune responses and virus control.