title: Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice.
abstract: Defence mechanisms against intracellular bacterial pathogens are incompletely understood. Our study characterizes a type I IFN-dependent cell-autonomous defence pathway directed against Legionella pneumophila, an intracellular model organism and frequent cause of pneumonia. We show that macrophages infected with L. pneumophila produced IFNβ in a STING- and IRF3- dependent manner. Paracrine type I IFNs stimulated upregulation of IFN-stimulated genes and a cell-autonomous defence pathway acting on replicating and non-replicating Legionella within their specialized vacuole. Our infection experiments in mice lacking receptors for type I and/or II IFNs show that type I IFNs contribute to expression of IFN-stimulated genes and to bacterial clearance as well as resistance in L. pneumophila pneumonia in addition to type II IFN. Overall, our study shows that paracrine type I IFNs mediate defence against L. pneumophila, and demonstrates a protective role of type I IFNs in in vivo infections with intracellular bacteria.
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Lippmann
authors.forename: Holger C
authors.initials: HC
authors.lastname: Müller
authors.forename: Jan
authors.initials: J
authors.lastname: Naujoks
authors.forename: Christoph
authors.initials: C
authors.lastname: Tabeling
authors.forename: Sunny
authors.initials: S
authors.lastname: Shin
authors.forename: Martin
authors.initials: M
authors.lastname: Witzenrath
authors.forename: Katharina
authors.initials: K
authors.lastname: Hellwig
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Taylor
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology*; D016952:Legionella pneumophila / Q000276:immunology* / Q000472:pathogenicity*; D007877:Legionnaires' Disease / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D014617:Vacuoles / Q000276:immunology / Q000382:microbiology; D000099197:STING Protein
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D008565:Membrane Proteins; C494233:Irf3 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein