title: Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue.
abstract: Coxiella burnetii is an intracellular pathogen and the cause of Q fever. Gamma interferon (IFN-γ) is critical for host protection from infection, but a role for type I IFN in C. burnetii infection has not been determined. Type I IFN supports host protection from a related pathogen, Legionella pneumophila, and we hypothesized that it would be similarly protective in C. burnetii infection. In contrast to our prediction, IFN-α receptor-deficient (IFNAR(-/-)) mice were protected from C. burnetii-induced infection. Therefore, the role of type I IFN in C. burnetii infection was distinct from that in L. pneumophila Mice treated with a double-stranded-RNA mimetic were protected from C. burnetii-induced weight loss through an IFNAR-independent pathway. We next treated mice with recombinant IFN-α (rIFN-α). When rIFN-α was injected by the intraperitoneal route during infection, disease-induced weight loss was exacerbated. Mice that received rIFN-α by this route had dampened interleukin 1β (IL-1β) expression in bronchoalveolar lavage fluids. However, when rIFN-α was delivered to the lung, bacterial replication was decreased in all tissues. Thus, the presence of type I IFN in the lung protected from infection, but when delivered to the periphery, type I IFN enhanced disease, potentially by dampening inflammatory cytokines. To better characterize the capacity for type I IFN induction by C. burnetii, we assessed expression of IFN-β transcripts by human macrophages following stimulation with lipopolysaccharide (LPS) from C. burnetii Understanding innate responses in C. burnetii infection will support the discovery of novel therapies that may be alternative or complementary to the current antibiotic treatment.
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA jodi.hedges@gmail.com.
authors.forename: Jodi F
authors.initials: JF
authors.lastname: Hedges
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Robison
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Kimmel
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Lucas
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ramstead
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jutila
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D016997:Coxiella burnetii / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D016952:Legionella pneumophila / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D011778:Q Fever / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D053633:Receptor, Interferon alpha-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction; D015431:Weight Loss / Q000187:drug effects
chemical_list: D052157:Aptamers, Nucleotide; C587672:IL1B protein, mouse; C508032:Ifnar1 protein, mouse; D016898:Interferon-alpha; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta