title: Too much of a good thing: Sustained type 1 interferon signaling limits humoral responses to secondary viral infection.
abstract: The induction of a pan-immunosuppressive state is a central feature of persistent viral infections. Over the past decade, multiple pathways have been identified that contribute to immune suppression. Recently, it was revealed that aberrant or sustained type 1 interferon (IFN-I) production or signaling is a central contributor to immune suppression elicited during persistent viral infection. In this issue, Honke et al. [Eur. J. Immunol. 2016. 46: 372-380] identify that IFN-I signaling promotes an immune suppressive state during persistent lymphocytic choriomeningitis virus infection by inhibiting enforced virus replication in CD169(+) macrophages. The authors demonstrate that mice infected with a persistent strain of lymphocytic choriomeningitis virus have blunted humoral immune responses to a superinfecting vesicular stomatitis virus infection. The absence of virus replication in CD169(+) macrophages was not due to antiviral CD8(+) T cell-mediated killing of CD169(+) macrophages, but required sustained IFN-I responses. In turn, reduction in vesicular stomatitis virus replication in CD169(+) macrophages resulted in a reduction in antigen production, which is necessary for generating optimal humoral responses. This study highlights a novel mechanism by which IFN-I signaling promotes an immune suppressive state during persistent viral infection.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.|Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teijaro
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D007165:Immunosuppression Therapy; D007370:Interferon Type I / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D051379:Mice; D015398:Signal Transduction; D015163:Superinfection / Q000276:immunology*; D054243:Vesicular Stomatitis / Q000276:immunology*; D018116:Vesiculovirus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007370:Interferon Type I
keywords: Chronic infection; Lymphocytic choriomeningitis virus; Macrophages; Type I Interferon; Vesicular stomatitis virus