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The Journal of Immunology, 2004, 172: 6894-6901.
Copyright © 2004 by The American Association of Immunologists

Production of IFN-{gamma} by CD4 T Cells Is Essential for Resolving Ehrlichia Infection1

Constantine Bitsaktsis*, Jennifer Huntington* and Gary Winslow2,*,{dagger}

* Wadsworth Center, New York State Department of Health, Albany, NY 12201; and {dagger} Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, NY 12201

To address the role of cellular immunity during ehrlichia infection, we have used a newly described model of monocytic ehrlichiosis that results from infection of mice by an ehrlichia that was isolated from an Ixodes ovatus tick (Ixodes ovatus ehrlichia, IOE). Immunocompetent C57BL/6 and BALB/c mice exhibited a dose-dependent susceptibility to IOE infection. Mice infected with a high dose inoculum (~1000 organisms) exhibited pronounced thrombocytopenia, lymphopenia, anemia, and morbidity within 12 days postinfection. Infection was associated with bacterial colonization of a number of tissues. In contrast, mice infected with a low dose inoculum (~100 organisms) exhibited only transient disease and were able to resolve the infection. SCID mice were highly susceptible to low-dose infection, indicating that adaptive immunity was required. Resistance to sublethal challenge in both C57BL/6 and BALB/c mice was CD4-, but not CD8-, dependent and required IL-12p40-dependent cytokines, IFN-{gamma}, and TNF-{alpha}, but not IL-4. CD4 T cells purified from infected mice proliferated in vitro in response to IOE Ags. T cell proliferation was associated with production of IFN-{gamma}, and the production of this cytokine by CD4 T cells rescued IFN-{gamma}-deficient mice from fatal infection. Exogenous IFN-{gamma} was capable of inducing microbiocidal activity in infected macrophages. The data suggest that classical immune mechanisms involving CD4 cells and type 1 cytokines are responsible for macrophage activation and for elimination of this intracellular bacterial pathogen.




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