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

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 l...

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Autores principales:	Thomas P Burke, Patrik Engström, Cuong J Tran, Ingeborg M Langohr, Dustin R Glasner, Diego A Espinosa, Eva Harris, Matthew D Welch
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	interferons eschar-associated rickettsiosis rickettsia actin-based motility type i interferon immunity Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/07eddd4f03e24d1f84e96e5ba2c2bb6f
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spelling	oai:doaj.org-article:07eddd4f03e24d1f84e96e5ba2c2bb6f2021-11-15T16:49:53ZInterferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis10.7554/eLife.670292050-084Xe67029https://doaj.org/article/07eddd4f03e24d1f84e96e5ba2c2bb6f2021-08-01T00:00:00Zhttps://elifesciences.org/articles/67029https://doaj.org/toc/2050-084XArthropod-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.Thomas P BurkePatrik EngströmCuong J TranIngeborg M LangohrDustin R GlasnerDiego A EspinosaEva HarrisMatthew D WelcheLife Sciences Publications Ltdarticleinterferonseschar-associated rickettsiosisrickettsiaactin-based motilitytype i interferonimmunityMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	interferons eschar-associated rickettsiosis rickettsia actin-based motility type i interferon immunity Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	interferons eschar-associated rickettsiosis rickettsia actin-based motility type i interferon immunity Medicine R Science Q Biology (General) QH301-705.5 Thomas P Burke Patrik Engström Cuong J Tran Ingeborg M Langohr Dustin R Glasner Diego A Espinosa Eva Harris Matthew D Welch Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
description	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.
format	article
author	Thomas P Burke Patrik Engström Cuong J Tran Ingeborg M Langohr Dustin R Glasner Diego A Espinosa Eva Harris Matthew D Welch
author_facet	Thomas P Burke Patrik Engström Cuong J Tran Ingeborg M Langohr Dustin R Glasner Diego A Espinosa Eva Harris Matthew D Welch
author_sort	Thomas P Burke
title	Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
title_short	Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
title_full	Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
title_fullStr	Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
title_full_unstemmed	Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
title_sort	interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/07eddd4f03e24d1f84e96e5ba2c2bb6f
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Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

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