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Infection and Immunity, May 2001, p. 3359-3371, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3359-3371.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Coinfection with Borrelia burgdorferi and the Agent of Human Granulocytic Ehrlichiosis Alters Murine Immune Responses, Pathogen Burden, and Severity of Lyme Arthritis

Venetta Thomas,1 Juan Anguita,1 Stephen W. Barthold,2 and Erol Fikrig1,*

Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520,1 and Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California, Davis, California 956162

Received 4 December 2000/Returned for modification 17 January 2001/Accepted 30 January 2001

Lyme disease and human granulocytic ehrlichiosis (HGE) are tick-borne illnesses caused by Borrelia burgdorferi and the agent of HGE, respectively. We investigated the influence of dual infection with B. burgdorferi and the HGE agent on the course of murine Lyme arthritis and granulocytic ehrlichiosis. Coinfection resulted in increased levels of both pathogens and more severe Lyme arthritis compared with those in mice infected with B. burgdorferi alone. The increase in bacterial burden during dual infection was associated with enhanced acquisition of both organisms by larval ticks that were allowed to engorge upon infected mice. Coinfection also resulted in diminished interleukin-12 (IL-12), gamma interferon (IFN-gamma ), and tumor necrosis factor alpha levels and elevated IL-6 levels in murine sera. During dual infection, IFN-gamma receptor expression on macrophages was also reduced, implying a decrease in phagocyte activation. These results suggest that coinfection of mice with B. burgdorferi and the HGE agent modulates host immune responses, resulting in increased bacterial burden, Lyme arthritis, and pathogen transmission to the vector.

* Corresponding author. Mailing address: Yale University School of Medicine, Section of Rheumatology, Department of Internal Medicine, 608 Laboratory of Clinical Investigation, P.O. Box 208031, New Haven, CT 06520-8031. Phone: (203) 785-2453. Fax: (203) 785-7053. E-mail: erol.fikrig{at}yale.edu.

Infection and Immunity, May 2001, p. 3359-3371, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3359-3371.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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