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Updated: Jun 19, 2026
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Published on: July 16, 2019
Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
Thomas P Burke1, Patrik Engström1, Cuong J Tran1,2
1Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
Abstract:
Arthropod-borne rickettsial pathogens cause mild and severe human disease worldwide. The tick-borne pathogen Rickettsia parkeri elicits skin lesions (eschars) and disseminated disease in humans; however, inbred mice are generally resistant to infection. We report that intradermal infection of mice lacking both interferon receptors (Ifnar1-/-;Ifngr1-/-) with as few as 10 R. 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. Immunizing Ifnar1-/-;Ifngr1-/- mice with sca2 and ompB mutant R. 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.
Insights
Mice lacking interferon receptors are susceptible to Rickettsia parkeri infection, forming skin lesions and developing lethal disease. This model aids in studying tick-borne rickettsiosis and identifying potential live-attenuated vaccine candidates.
Area of Science:
- Microbiology
- Immunology
- Pathogen Research
Background:
- Arthropod-borne rickettsial pathogens cause significant human disease globally.
- Rickettsia parkeri, a tick-borne bacterium, causes eschars and disseminated illness in humans.
- Inbred mice typically exhibit resistance to R. parkeri infection, limiting disease modeling.
Purpose of the Study:
- To establish a murine model for studying R. parkeri pathogenesis and host-pathogen interactions.
- To investigate the roles of bacterial factors in disease development.
- To identify potential vaccine candidates against R. parkeri infections.
Main Methods:
- Intradermal inoculation of R. parkeri into interferon receptor-deficient (Ifnar1) mice.
- Analysis of eschar formation, bacterial dissemination, and host immune responses.
- Generation and testing of sca2 and ompB mutant R. parkeri strains for vaccine potential.
Main Results:
- Ifnar1 mice infected with low doses of R. parkeri developed eschars and lethal disseminated disease, mimicking human infection.
- Bacterial dissemination from the skin was dependent on the actin-based motility factor Sca2.
- The outer membrane protein OmpB was crucial for eschar formation.
- Immunization with sca2 and ompB mutant strains conferred protection against subsequent R. parkeri challenge.
Conclusions:
- Ifnar1 mice provide a valuable model for rickettsiosis research, enabling study of virulence factors and immunity.
- Sca2 and OmpB are key virulence factors for R. parkeri dissemination and pathogenesis.
- Live-attenuated R. parkeri mutants deficient in Sca2 and OmpB represent promising vaccine candidates.
