Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428839/ https://www.ncbi.nlm.nih.gov/pubmed/34423779 http://dx.doi.org/10.7554/eLife.67029 |
_version_ | 1783750450027167744 |
---|---|
author | Burke, Thomas P Engström, Patrik Tran, Cuong J Langohr, Ingeborg M Glasner, Dustin R Espinosa, Diego A Harris, Eva Welch, Matthew D |
author_facet | Burke, Thomas P Engström, Patrik Tran, Cuong J Langohr, Ingeborg M Glasner, Dustin R Espinosa, Diego A Harris, Eva Welch, Matthew D |
author_sort | Burke, Thomas P |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8428839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-84288392021-09-13 Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis Burke, Thomas P Engström, Patrik Tran, Cuong J Langohr, Ingeborg M Glasner, Dustin R Espinosa, Diego A Harris, Eva Welch, Matthew D eLife Microbiology and Infectious Disease 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. eLife Sciences Publications, Ltd 2021-08-23 /pmc/articles/PMC8428839/ /pubmed/34423779 http://dx.doi.org/10.7554/eLife.67029 Text en © 2021, Burke et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Microbiology and Infectious Disease Burke, Thomas P Engström, Patrik Tran, Cuong J Langohr, Ingeborg M Glasner, Dustin R Espinosa, Diego A Harris, Eva Welch, Matthew D Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis |
title | 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_short | Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis |
title_sort | interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis |
topic | Microbiology and Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428839/ https://www.ncbi.nlm.nih.gov/pubmed/34423779 http://dx.doi.org/10.7554/eLife.67029 |
work_keys_str_mv | AT burkethomasp interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis AT engstrompatrik interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis AT trancuongj interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis AT langohringeborgm interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis AT glasnerdustinr interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis AT espinosadiegoa interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis AT harriseva interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis AT welchmatthewd interferonreceptordeficientmicearesusceptibletoescharassociatedrickettsiosis |