A Hematogenously Disseminated Orientia tsutsugamsushi-Infected Murine Model of Scrub Typhus

Thomas Shelite, Tais Saito, Nicole L. Mendell, Bin Gong, Guang Xu, Lynn Soong, Gustavo Valbuena, Donald Bouyer, David Walker

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 1.25×106 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.

Original languageEnglish (US)
Article numbere2966
JournalPLoS Neglected Tropical Diseases
Volume8
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Scrub Typhus
Orientia tsutsugamushi
Infection
Inbred C57BL Mouse
Trombiculidae
Pathology
Rickettsia
Meningoencephalitis
Mites
Interstitial Lung Diseases
Disease Progression
Immunity
Endothelial Cells
Staining and Labeling
Hemorrhage
Antigens
Lung
Brain

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

A Hematogenously Disseminated Orientia tsutsugamsushi-Infected Murine Model of Scrub Typhus. / Shelite, Thomas; Saito, Tais; Mendell, Nicole L.; Gong, Bin; Xu, Guang; Soong, Lynn; Valbuena, Gustavo; Bouyer, Donald; Walker, David.

In: PLoS Neglected Tropical Diseases, Vol. 8, No. 7, e2966, 2014.

Research output: Contribution to journalArticle

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