Murine models of scrub typhus associated with host control of Orientia tsutsugamushi infection

Nicole L. Mendell, Donald Bouyer, David Walker

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Scrub typhus, a febrile illness of substantial incidence and mortality, is caused by infection with the obligately intracellular bacterium Orientia tsutsugamushi. It is estimated that there are more than one million cases annually transmitted by the parasitic larval stage of trombiculid mites in the Asia-Pacific region. The antigenic and genetic diversity of the multiple strains of O. tsutsugamushi hinders the advancement of laboratory diagnosis, development of long-lasting vaccine-induced protection, and interpretation of clinical infection. Despite the life-threatening severity of the illness in hundreds of thousands of cases annually, 85–93% of patients survive, often without anti-rickettsial treatment. To more completely understand the disease caused by Orientia infection, animal models which closely correlate with the clinical manifestations, target cells, organ involvement, and histopathologic lesions of human cases of scrub typhus should be employed. Previously, our laboratory has extensively characterized two relevant C57BL/6 mouse models using O. tsutsugamushi Karp strain: a route-specific intradermal model of infection and persistence and a hematogenously disseminated dose-dependent lethal model. Principal findings: To complement the lethal model, here we illustrate a sublethal model in the same mouse strain using the O. tsutsugamushi Gilliam strain, which resulted in dose-dependent severity of illness, weight loss, and systemic dissemination to endothelial cells of the microcirculation and mononuclear phagocytic cells. Histopathologic lesions included expansion of the pulmonary interstitium by inflammatory cell infiltrates and multifocal hepatic lesions with mononuclear cellular infiltrates, renal interstitial lymphohistiocytic inflammation, mild meningoencephalitis, and characteristic typhus nodules. Significance: These models parallel characteristics of human cases of scrub typhus, and will be used in concert to understand differences in severity which lead to lethality or host control of the infection and to address the explanation for short duration of heterologous immunity in Orientia infection.

Original languageEnglish (US)
Article numbere0005453
JournalPLoS Neglected Tropical Diseases
Volume11
Issue number3
DOIs
StatePublished - Mar 10 2017

Fingerprint

Orientia tsutsugamushi
Scrub Typhus
Infection
Heterologous Immunity
Trombiculidae
Epidemic Louse-Borne Typhus
Antigenic Variation
Meningoencephalitis
Clinical Laboratory Techniques
Microcirculation
Phagocytes
Infection Control
Inbred C57BL Mouse
Weight Loss
Fever
Vaccines
Endothelial Cells
Animal Models
Inflammation
Bacteria

ASJC Scopus subject areas

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

Cite this

Murine models of scrub typhus associated with host control of Orientia tsutsugamushi infection. / Mendell, Nicole L.; Bouyer, Donald; Walker, David.

In: PLoS Neglected Tropical Diseases, Vol. 11, No. 3, e0005453, 10.03.2017.

Research output: Contribution to journalArticle

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