Animal Model of Fatal Human Monocytotropic Ehrlichiosis

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2001 Feb 13

PMID 11159213

Citations 45

Authors

E A Sotomayor

V L Popov

H M Feng

D H Walker

J P Olano

Affiliations

Soon will be listed here.

Abstract

Human monocytotropic ehrlichiosis caused by Ehrlichia chaffeensis is a life-threatening, tick-borne, emerging infectious disease for which no satisfactory animal model has been developed. Strain HF565, an ehrlichial organism closely related to E. chaffeensis isolated from Ixodes ovatus ticks in Japan, causes fatal infection of mice. C57BL/6 mice became ill on day 7 after inoculation and died on day 9. The liver revealed confluent necrosis, ballooning cell injury, apoptosis, poorly formed granulomas, Kupffer cell hyperplasia, erythrophagocytosis, and microvesicular fatty metamorphosis. The other significant histological findings consisted of marked expansion of the marginal zone and infiltration of the red pulp of the spleen by macrophages, interstitial pneumonitis, and increased numbers of immature myeloid cells and areas of necrosis in the bone marrow. Ehrlichiae were detected by immunohistology and electron microscopy in the liver, lungs, and spleen. The main target cells were macrophages, including Kupffer cells, hepatocytes, and endothelial cells. Apoptosis was detected in Kupffer cells, hepatocytes, and macrophages in the lungs and spleen. This tropism for macrophages and the pathological lesions closely resemble those of human monocytotropic ehrlichiosis for which it is a promising model for investigation of immunity and pathogenesis.

Citing Articles

RipE expression correlates with high ATP levels in , which confers resistance during the extracellular stage to facilitate a new cycle of infection.

Chien R, Lin M, Duan N, Denton S, Kawahara J, Rikihisa Y Front Cell Infect Microbiol. 2024; 14:1416577.

PMID: 39411319 PMC: 11473500. DOI: 10.3389/fcimb.2024.1416577.

effector TRP120 manipulates bacteremia to facilitate tick acquisition.

Zhang T, Chien R, Budachetri K, Lin M, Boyaka P, Huang W mBio. 2024; 15(4):e0047624.

PMID: 38501870 PMC: 11005420. DOI: 10.1128/mbio.00476-24.

Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis.

Sharma A, Ismail N Cells. 2023; 12(22).

PMID: 37998332 PMC: 10670716. DOI: 10.3390/cells12222597.

Evasion of host antioxidative response via disruption of NRF2 signaling in fatal Ehrlichia-induced liver injury.

Sharma A, El Andaloussi A, Ismail N PLoS Pathog. 2023; 19(11):e1011791.

PMID: 37956169 PMC: 10681308. DOI: 10.1371/journal.ppat.1011791.

Review: Protective Immunity and Immunopathology of Ehrlichiosis.

Ismail N, Sharma A, Soong L, Walker D Zoonoses (Burlingt). 2022; 2(1).

PMID: 35876763 PMC: 9300479. DOI: 10.15212/zoonoses-2022-0009.

References

McQuiston J, Paddock C, Holman R, Childs J . The human ehrlichioses in the United States. Emerg Infect Dis. 1999; 5(5):635-42. PMC: 2627718. DOI: 10.3201/eid0505.990504. View

Clifton D, Goss R, Sahni S, Van Antwerp D, Baggs R, Marder V . NF-kappa B-dependent inhibition of apoptosis is essential for host cellsurvival during Rickettsia rickettsii infection. Proc Natl Acad Sci U S A. 1998; 95(8):4646-51. PMC: 22544. DOI: 10.1073/pnas.95.8.4646. View

Weaver R, Virella G, Weaver A . Ehrlichiosis with severe pulmonary manifestations despite early treatment. South Med J. 1999; 92(3):336-9. DOI: 10.1097/00007611-199903000-00018. View

Fishbein D, Kemp A, DAWSON J, Greene N, Redus M, Fields D . Human ehrlichiosis: prospective active surveillance in febrile hospitalized patients. J Infect Dis. 1989; 160(5):803-9. DOI: 10.1093/infdis/160.5.803. View

Walker D, Dumler J . Human monocytic and granulocytic ehrlichioses. Discovery and diagnosis of emerging tick-borne infections and the critical role of the pathologist. Arch Pathol Lab Med. 1997; 121(8):785-91. View

Marty A, Dumler J, Imes G, Brusman H, Smrkovski L, Frisman D . Ehrlichiosis mimicking thrombotic thrombocytopenic purpura. Case report and pathological correlation. Hum Pathol. 1995; 26(8):920-5. DOI: 10.1016/0046-8177(95)90017-9. View

Anderson B, DAWSON J, Jones D, WILSON K . Ehrlichia chaffeensis, a new species associated with human ehrlichiosis. J Clin Microbiol. 1991; 29(12):2838-42. PMC: 270443. DOI: 10.1128/jcm.29.12.2838-2842.1991. View

Maeda K, Markowitz N, Hawley R, Ristic M, Cox D, McDade J . Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med. 1987; 316(14):853-6. DOI: 10.1056/NEJM198704023161406. View

Eng T, Harkess J, Fishbein D, DAWSON J, Greene C, Redus M . Epidemiologic, clinical, and laboratory findings of human ehrlichiosis in the United States, 1988. JAMA. 1990; 264(17):2251-8. View

10.

Hildebrandt P, Huxsoll D, Walker J, NIMS R, Taylor R, Andrews M . Pathology of canine ehrlichiosis (tropical canine pancytopenia). Am J Vet Res. 1973; 34(10):1309-20. View

11.

Winslow G, Yager E, Shilo K, Collins D, Chu F . Infection of the laboratory mouse with the intracellular pathogen Ehrlichia chaffeensis. Infect Immun. 1998; 66(8):3892-9. PMC: 108445. DOI: 10.1128/IAI.66.8.3892-3899.1998. View

12.

Yoshiie K, Kim H, Mott J, Rikihisa Y . Intracellular infection by the human granulocytic ehrlichiosis agent inhibits human neutrophil apoptosis. Infect Immun. 2000; 68(3):1125-33. PMC: 97257. DOI: 10.1128/IAI.68.3.1125-1133.2000. View

13.

Fichtenbaum C, Peterson L, Weil G . Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome. Am J Med. 1993; 95(4):351-7. DOI: 10.1016/0002-9343(93)90302-6. View

14.

Groves M, Dennis G, Amyx H, Huxsoll D . Transmission of Ehrlichia canis to dogs by ticks (Rhipicephalus sanguineus). Am J Vet Res. 1975; 36(7):937-40. View

15.

Vugia D, Holmberg E, Steffe E, Ascher M, Gallo D . A human case of monocytic ehrlichiosis with adult respiratory distress syndrome in northern California. West J Med. 1996; 164(6):525-8. PMC: 1303637. View

16.

EVERETT E, Evans K, HENRY R, McDonald G . Human ehrlichiosis in adults after tick exposure. Diagnosis using polymerase chain reaction. Ann Intern Med. 1994; 120(9):730-5. DOI: 10.7326/0003-4819-120-9-199405010-00002. View

17.

Bunnell J, Trigiani E, Srinivas S, Dumler J . Development and distribution of pathologic lesions are related to immune status and tissue deposition of human granulocytic ehrlichiosis agent-infected cells in a murine model system. J Infect Dis. 1999; 180(2):546-50. DOI: 10.1086/314902. View

18.

Anziani O, Ewing S, Barker R . Experimental transmission of a granulocytic form of the tribe Ehrlichieae by Dermacentor variabilis and Amblyomma americanum to dogs. Am J Vet Res. 1990; 51(6):929-31. View

19.

Kawahara M, Suto C, Rikihisa Y, Yamamoto S, Tsuboi Y . Characterization of ehrlichial organisms isolated from a wild mouse. J Clin Microbiol. 1993; 31(1):89-96. PMC: 262627. DOI: 10.1128/jcm.31.1.89-96.1993. View

20.

Bakken J, Krueth J, Tilden R, Asanovich K, Dumler J . Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA. 1996; 275(3):199-205. View