An animal model of a newly emerging human ehrlichiosis

Tais Saito, Nagaraja R. Thirumalapura, Thomas Shelite, Dedeke Rockx-Brouwer, Vsevolod Popov, David Walker

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background. Human ehrlichioses are emerging life-threatening diseases transmitted by ticks. Animal models have been developed to study disease development; however, there is no valid small animal model that uses a human ehrlichial pathogen. The objective of this study was to develop a mouse model for ehrlichiosis with the newly discovered human pathogen, Ehrlichia muris-like agent (EMLA). Methods.Three strains of mice were inoculated with different doses of EMLA by the intravenous, intraperitoneal, or intradermal route and evaluated for clinical and pathologic changes during the course of infection. Results.EMLA infected C57Bl/6, BALB/c, and C3H/HeN mice and induced lethal or persistent infection in a route-and dose-dependent manner. The clinical chemistry and hematologic changes were similar to those of human infection by Ehrlichia chaffeensis or EMLA. Bacterial distribution in tissues differed after intradermal infection, compared with the distribution after intravenous or intraperitoneal injection. Lethal infection did not cause remarkable pathologic changes, but it caused fluid imbalance. EMLA infection of endothelium and mononuclear cells likely plays a role in the severe outcome. Conclusions.The EMLA mouse model mimics human infection and can be used to study pathogenesis and immunity and for development of a vector transmission model of ehrlichiosis.

Original languageEnglish (US)
Pages (from-to)452-461
Number of pages10
JournalJournal of Infectious Diseases
Volume211
Issue number3
DOIs
StatePublished - Feb 1 2015

Fingerprint

Ehrlichiosis
Ehrlichia
Animal Models
Infection
Ehrlichia chaffeensis
Clinical Chemistry
Inbred C3H Mouse
Ticks
Tissue Distribution
Intraperitoneal Injections
Intravenous Injections
Endothelium
Immunity

Keywords

  • Ehrlichia muris-like
  • ehrlichiosis
  • emerging infectious disease
  • human pathogen
  • tick-borne disease

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

An animal model of a newly emerging human ehrlichiosis. / Saito, Tais; Thirumalapura, Nagaraja R.; Shelite, Thomas; Rockx-Brouwer, Dedeke; Popov, Vsevolod; Walker, David.

In: Journal of Infectious Diseases, Vol. 211, No. 3, 01.02.2015, p. 452-461.

Research output: Contribution to journalArticle

Saito, Tais ; Thirumalapura, Nagaraja R. ; Shelite, Thomas ; Rockx-Brouwer, Dedeke ; Popov, Vsevolod ; Walker, David. / An animal model of a newly emerging human ehrlichiosis. In: Journal of Infectious Diseases. 2015 ; Vol. 211, No. 3. pp. 452-461.
@article{f67f30354b9d40cb9adf2e4442199c21,
title = "An animal model of a newly emerging human ehrlichiosis",
abstract = "Background. Human ehrlichioses are emerging life-threatening diseases transmitted by ticks. Animal models have been developed to study disease development; however, there is no valid small animal model that uses a human ehrlichial pathogen. The objective of this study was to develop a mouse model for ehrlichiosis with the newly discovered human pathogen, Ehrlichia muris-like agent (EMLA). Methods.Three strains of mice were inoculated with different doses of EMLA by the intravenous, intraperitoneal, or intradermal route and evaluated for clinical and pathologic changes during the course of infection. Results.EMLA infected C57Bl/6, BALB/c, and C3H/HeN mice and induced lethal or persistent infection in a route-and dose-dependent manner. The clinical chemistry and hematologic changes were similar to those of human infection by Ehrlichia chaffeensis or EMLA. Bacterial distribution in tissues differed after intradermal infection, compared with the distribution after intravenous or intraperitoneal injection. Lethal infection did not cause remarkable pathologic changes, but it caused fluid imbalance. EMLA infection of endothelium and mononuclear cells likely plays a role in the severe outcome. Conclusions.The EMLA mouse model mimics human infection and can be used to study pathogenesis and immunity and for development of a vector transmission model of ehrlichiosis.",
keywords = "Ehrlichia muris-like, ehrlichiosis, emerging infectious disease, human pathogen, tick-borne disease",
author = "Tais Saito and Thirumalapura, {Nagaraja R.} and Thomas Shelite and Dedeke Rockx-Brouwer and Vsevolod Popov and David Walker",
year = "2015",
month = "2",
day = "1",
doi = "10.1093/infdis/jiu372",
language = "English (US)",
volume = "211",
pages = "452--461",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - An animal model of a newly emerging human ehrlichiosis

AU - Saito, Tais

AU - Thirumalapura, Nagaraja R.

AU - Shelite, Thomas

AU - Rockx-Brouwer, Dedeke

AU - Popov, Vsevolod

AU - Walker, David

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Background. Human ehrlichioses are emerging life-threatening diseases transmitted by ticks. Animal models have been developed to study disease development; however, there is no valid small animal model that uses a human ehrlichial pathogen. The objective of this study was to develop a mouse model for ehrlichiosis with the newly discovered human pathogen, Ehrlichia muris-like agent (EMLA). Methods.Three strains of mice were inoculated with different doses of EMLA by the intravenous, intraperitoneal, or intradermal route and evaluated for clinical and pathologic changes during the course of infection. Results.EMLA infected C57Bl/6, BALB/c, and C3H/HeN mice and induced lethal or persistent infection in a route-and dose-dependent manner. The clinical chemistry and hematologic changes were similar to those of human infection by Ehrlichia chaffeensis or EMLA. Bacterial distribution in tissues differed after intradermal infection, compared with the distribution after intravenous or intraperitoneal injection. Lethal infection did not cause remarkable pathologic changes, but it caused fluid imbalance. EMLA infection of endothelium and mononuclear cells likely plays a role in the severe outcome. Conclusions.The EMLA mouse model mimics human infection and can be used to study pathogenesis and immunity and for development of a vector transmission model of ehrlichiosis.

AB - Background. Human ehrlichioses are emerging life-threatening diseases transmitted by ticks. Animal models have been developed to study disease development; however, there is no valid small animal model that uses a human ehrlichial pathogen. The objective of this study was to develop a mouse model for ehrlichiosis with the newly discovered human pathogen, Ehrlichia muris-like agent (EMLA). Methods.Three strains of mice were inoculated with different doses of EMLA by the intravenous, intraperitoneal, or intradermal route and evaluated for clinical and pathologic changes during the course of infection. Results.EMLA infected C57Bl/6, BALB/c, and C3H/HeN mice and induced lethal or persistent infection in a route-and dose-dependent manner. The clinical chemistry and hematologic changes were similar to those of human infection by Ehrlichia chaffeensis or EMLA. Bacterial distribution in tissues differed after intradermal infection, compared with the distribution after intravenous or intraperitoneal injection. Lethal infection did not cause remarkable pathologic changes, but it caused fluid imbalance. EMLA infection of endothelium and mononuclear cells likely plays a role in the severe outcome. Conclusions.The EMLA mouse model mimics human infection and can be used to study pathogenesis and immunity and for development of a vector transmission model of ehrlichiosis.

KW - Ehrlichia muris-like

KW - ehrlichiosis

KW - emerging infectious disease

KW - human pathogen

KW - tick-borne disease

UR - http://www.scopus.com/inward/record.url?scp=84922572870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922572870&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiu372

DO - 10.1093/infdis/jiu372

M3 - Article

VL - 211

SP - 452

EP - 461

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 3

ER -