Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue

Abstract

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.