Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

We report that intradermal infection of mice lacking both interferon receptors (Ifnar1-/-;Ifngr1-/-) with as few as 10R. parkeri elicits eschar formation and disseminated, lethal disease. Similar to human infection, eschars exhibited necrosis and inflammation, with bacteria primarily found in leukocytes. Using this model, we find that the actin-based motility factor Sca2 is required for dissemination from the skin to internal organs, and the outer membrane protein OmpB contributes to eschar formation. ImmunizingIfnar1-/-;Ifngr1-/- mice withsca2 andompB mutantR. parkeri protects against rechallenge, revealing live-attenuated vaccine candidates. Thus,Ifnar1-/-;Ifngr1-/- mice are a tractable model to investigate rickettsiosis, virulence factors, and immunity. Our results further suggest that discrepancies between mouse and human susceptibility may be due to differences in interferon signaling.
Source: eLife - Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research