title: Disease-promoting effects of type I interferons in viral, bacterial, and coinfections.
abstract: While type I interferons (IFNs) are universally acknowledged for their antiviral and immunostimulatory functions, there is increasing appreciation of the detrimental effects of inappropriate, excessive, or mistimed type I IFN responses in viral and bacterial infections. The underlying mechanisms by which type I IFNs promote susceptibility or severity include direct tissue damage by apoptosis induction or suppression of proliferation in tissue cells, immunopathology due to excessive inflammation, and cell death induced by TRAIL- and Fas-expressing immune cells, as well as immunosuppression through IL-10, IL-27, PD-L1, IL-1Ra, and other regulatory molecules that antagonize the induction or action of IL-1, IL-12, IL-17, IFN-γ, KC, and other effectors of the immune response. Bacterial superinfections following influenza infection are a prominent example of a situation where type I IFNs can misdirect the immune response. This review discusses current understanding of the parameters of signal strength, duration, timing, location, and cellular recipients that determine whether type I IFNs have beneficial or detrimental effects in infection.
authors.affiliation: 1 Division of Immunoregulation, MRC National Institute for Medical Research , Mill Hill, London, United Kingdom .
authors.forename: Sophia
authors.initials: S
authors.lastname: Davidson
authors.forename: Mala K
authors.initials: MK
authors.lastname: Maini
authors.forename: Andreas
authors.initials: A
authors.lastname: Wack
mesh_terms: D001424:Bacterial Infections / Q000276:immunology / Q000503:physiopathology*; D060085:Coinfection / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology / Q000503:physiopathology*
chemical_list: D007370:Interferon Type I