Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue.
Infect Immun
; 84(6): 1815-1825, 2016 06.
Article
in En
| MEDLINE
| ID: mdl-27068091
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 1ß (IL-1ß) 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-ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Q Fever
/
Interferon-alpha
/
Coxiella burnetii
/
Receptor, Interferon alpha-beta
/
Host-Pathogen Interactions
Type of study:
Prognostic_studies
Language:
En
Journal:
Infect Immun
Year:
2016
Type:
Article
Affiliation country:
United States