Type I IFN signaling promotes Coxiella burnetii infection (INM8P.446)

• Published in: The Journal of immunology (1950) Vol. 192; no. 1_Supplement; pp. 124 - 124.12
• Main Authors: Hedges, Jodi, Robison, Amanda, Christensen, Kelly, Ramstead, Andrew, Jutila, Mark
• Format: Journal Article
• Language: English
• Published: 01-05-2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.124.12

Coxiella burnetii is an obligate intracellular pathogen and the cause of Q fever. The strain Nine Mile Phase I (NMI) is virulent whereas a laboratory passaged avirulent form is referred to as Phase II (NMII). Interferon (IFN)-γ is critical for protection from C. burnetii, but a role for type I IFN has not been determined. Type I IFN supports host protection from a related pathogen, Legionella pneumophila, thus we hypothesized that it would be similarly protective in C. burnetii infection. When murine macrophages were treated with IFN-α in vitro at infection, replication of NMII decreased, however, treatment 24 hours post-infection enhanced replication. Infection of spleen cells from type I IFN receptor (IFNAR)-deficient mice in vitro yielded fewer NMII genomic equivalents compared to wild type, with no change in IFN-γ expression. Thus, type I IFN signaling early in infection protected against NMII replication, but later signaling promoted replication. In vivo studies using the virulent NMI similarly suggested that IFNAR signaling promoted pathogenesis. IFNAR-deficient mice infected with NMI were significantly protected from weight loss compared to wild-type mice, although they had larger spleens and similar C. burnetii genomic equivalents. The data suggest that type I IFN signaling promotes infection with C. burnetii, contrary to the case with L. pneumophila. These results support abrogation of this pathway as a potential therapeutic approach to Q fever.