Affiliation:
1. Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA
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.
Funder
HHS | National Institutes of Health
M. J. Murdock Charitable Trust
Montana State University (MSU) Agricultural Experiment Station
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
15 articles.
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