title: Confounding roles for type I interferons during bacterial and viral pathogenesis.
abstract: Although type I interferons (IFN-I) were initially defined as potent antiviral agents, they can also cause decreased host resistance to some bacterial and viral infections. The many antiviral functions of the IFN-I include direct suppression of viral replication and activation of the immune response against viruses. In addition to their antiviral effects, IFN-I are also protective against several extracellular bacterial infections, in part, by promoting the induction of TNF-α and nitric oxide. In contrast, there is a negative effect of IFN-I on host resistance during chronic infection with lymphocytic choriomeningitis virus (LCMV) and acute infections with intracellular bacteria. In the case of LCMV, chronic IFN-I signaling induces adaptive immune system suppression. Blockade of IFN-I signaling removes the suppression and allows CD4 T-cell- and IFN-γ-mediated resolution of the infection. During acute intracellular bacterial infection, IFN-I suppress innate immunity by at least two defined mechanisms. During Francisella infection, IFN-I prevent IL-17 upregulation on γδ T cells and neutrophil recruitment. Following Listeria infection, IFN-I promote the cell death of macrophages and lymphocytes, which leads to innate immune suppression. These divergent findings for the role of IFN-I on pathogen control emphasize the complexity of the interferons system and force more mechanistic evaluation of its role in pathogenesis. This review evaluates IFN-I during infection with an emphasis on work carried out IFN-I-receptor-deficient mice.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Javier Antonio
authors.initials: JA
authors.lastname: Carrero
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D042541:Intracellular Space / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta
keywords: LCMV; Listeria monocytogenes; cytokine; infection; mouse