Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].

Orientia tsutsugamushi, the etiologic agent of scrub typhus, is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites. Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi, emphasizing its importance in global hea...

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Autores principales:	Thomas R Shelite, Tais B Saito, Nicole L Mendell, Bin Gong, Guang Xu, Lynn Soong, Gustavo Valbuena, Donald H Bouyer, David H Walker
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/60dd5a829a284f24a60af78bc4f49988
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spelling	oai:doaj.org-article:60dd5a829a284f24a60af78bc4f499882021-11-25T06:32:25ZHematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].1935-27271935-273510.1371/journal.pntd.0002966https://doaj.org/article/60dd5a829a284f24a60af78bc4f499882014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25010338/pdf/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Orientia tsutsugamushi, the etiologic agent of scrub typhus, is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites. Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi, emphasizing its importance in global health. In order to study scrub typhus, Orientia tsutsugamushi Karp strain has been used extensively in mouse studies with various inoculation strategies and little success in inducing disease progression similar to that of human scrub typhus. The objective of this project was to develop a disease model with pathology and target cells similar to those of severe human scrub typhus. This study reports an intravenous infection model of scrub typhus in C57BL/6 mice. This mouse strain was susceptible to intravenous challenge, and lethal infection occurred after intravenous inoculation of 1.25 × 10(6) focus (FFU) forming units. Signs of illness in lethally infected mice appeared on day 6 with death occurring ∼ 6 days later. Immunohistochemical staining for Orientia antigens demonstrated extensive endothelial infection, most notably in the lungs and brain. Histopathological analysis revealed cerebral perivascular, lymphohistiocytic infiltrates, focal hemorrhages, meningoencephalitis, and interstitial pneumonia. Disseminated infection of endothelial cells with Orientia in C57BL/6 mice resulted in pathology resembling that of human scrub typhus. The use of this model will allow detailed characterization of the mechanisms of immunity to and pathogenesis of O. tsutsugamushi infection.Thomas R SheliteTais B SaitoNicole L MendellBin GongGuang XuLynn SoongGustavo ValbuenaDonald H BouyerDavid H WalkerPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 8, Iss 7, p e2966 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Thomas R Shelite Tais B Saito Nicole L Mendell Bin Gong Guang Xu Lynn Soong Gustavo Valbuena Donald H Bouyer David H Walker Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
description	Orientia tsutsugamushi, the etiologic agent of scrub typhus, is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites. Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi, emphasizing its importance in global health. In order to study scrub typhus, Orientia tsutsugamushi Karp strain has been used extensively in mouse studies with various inoculation strategies and little success in inducing disease progression similar to that of human scrub typhus. The objective of this project was to develop a disease model with pathology and target cells similar to those of severe human scrub typhus. This study reports an intravenous infection model of scrub typhus in C57BL/6 mice. This mouse strain was susceptible to intravenous challenge, and lethal infection occurred after intravenous inoculation of 1.25 × 10(6) focus (FFU) forming units. Signs of illness in lethally infected mice appeared on day 6 with death occurring ∼ 6 days later. Immunohistochemical staining for Orientia antigens demonstrated extensive endothelial infection, most notably in the lungs and brain. Histopathological analysis revealed cerebral perivascular, lymphohistiocytic infiltrates, focal hemorrhages, meningoencephalitis, and interstitial pneumonia. Disseminated infection of endothelial cells with Orientia in C57BL/6 mice resulted in pathology resembling that of human scrub typhus. The use of this model will allow detailed characterization of the mechanisms of immunity to and pathogenesis of O. tsutsugamushi infection.
format	article
author	Thomas R Shelite Tais B Saito Nicole L Mendell Bin Gong Guang Xu Lynn Soong Gustavo Valbuena Donald H Bouyer David H Walker
author_facet	Thomas R Shelite Tais B Saito Nicole L Mendell Bin Gong Guang Xu Lynn Soong Gustavo Valbuena Donald H Bouyer David H Walker
author_sort	Thomas R Shelite
title	Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
title_short	Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
title_full	Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
title_fullStr	Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
title_full_unstemmed	Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
title_sort	hematogenously disseminated orientia tsutsugamushi-infected murine model of scrub typhus [corrected].
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/60dd5a829a284f24a60af78bc4f49988
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Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected].

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