title: Negative impact of IFN-γ on early host immune responses to retroviral infection.
abstract: 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.
authors: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors: Amanda K
authors: AK
authors: Duley
authors: Mickaël J-Y
authors: MJ
authors: Ploquin
authors: Urszula
authors: U
authors: Eksmond
authors: Christoph G
authors: CG
authors: Ammann
authors: Ronald J
authors: RJ
authors: Messer
authors: Lara
authors: L
authors: Myers
authors: Kim J
authors: KJ
authors: Hasenkrug
authors: George
authors: G
authors: Kassiotis
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology / Q000472:pathogenicity; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007772:Lactate dehydrogenase-elevating virus / Q000276:immunology / Q000472:pathogenicity; D009052:Leukemia Virus, Murine / Q000276:immunology* / Q000472:pathogenicity; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology / Q000821:virology; D051379:Mice; D020297:Mice, Congenic; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013155:Spleen Focus-Forming Viruses / Q000276:immunology / Q000472:pathogenicity; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology
chemical_list: D007371:Interferon-gamma