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Molecular and cellular pathobiology of Ehrlichia infection: targets for new therapeutics and immunomodulation strategies

Published online by Cambridge University Press:  31 January 2011

Jere W. McBride
Affiliation:
Department of Pathology, Center for Emerging Infectious Diseases and Biodefense, Sealy Center for Vaccine Development, and the Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
David H. Walker*
Affiliation:
Department of Pathology, Center for Emerging Infectious Diseases and Biodefense, Sealy Center for Vaccine Development, and the Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
*
*Corresponding author: David H. Walker, Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, USA. E-mail: dwalker@utmb.edu

Abstract

Ehrlichia are small obligately intracellular bacteria in the order Rickettsiales that are transmitted by ticks and associated with emerging life-threatening human zoonoses. Vaccines are not available for human ehrlichiosis, and therapeutic options are limited to a single antibiotic class. New technologies for exploring host–pathogen interactions have yielded recent advances in understanding the molecular interactions between Ehrlichia and the eukaryotic host cell and identified new targets for therapeutic and vaccine development, including those that target pathogen virulence mechanisms or disrupt the processes associated with ehrlichial effector proteins. Animal models have also provided insight into immunopathological mechanisms that contribute significantly to understanding severe disease manifestations, which should lead to the development of immunomodulatory approaches for treating patients nearing or experiencing severe disease states. In this review, we discuss the recent advances in our understanding of molecular and cellular pathobiology and the immunobiology of Ehrlichia infection. We identify new molecular host–pathogen interactions that can be targets of new therapeutics, and discuss prospects for treating the immunological dysregulation during acute infection that leads to life-threatening complications.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2011

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References

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Further reading, resources and contacts

Rikihisa, Y. (2010) Molecular events involved in cellular invasion by Ehrlichia chaffeensis and Anaplasma phagocytophilum. Veterinary Parastiology 167, 155-166CrossRefGoogle ScholarPubMed
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McBride, J.W. and Walker, D.H. (2010) Progress and obstacles in vaccine development for the ehrlichioses. Expert Review of Vaccines 9, 1071-1082CrossRefGoogle ScholarPubMed
Thomas, R.J., Dumler, J.S. and Carlyon, J.A. (2009) Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis. Expert Review of Anti-Infective Therapy 7, 709-722CrossRefGoogle ScholarPubMed