Production of IFN-gamma by CD4 T cells is essential for resolving ehrlichia infection.
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 ( approximately 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 ( approximately 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.
Bitsaktsis
Constantine
C
Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
Huntington
Jennifer
J
Winslow
Gary
G
D000740:Anemia / Q000209:etiology; D000818:Animals; D015704:CD4 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D004198:Disease Susceptibility; D016873:Ehrlichiosis / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018884:Ixodes / Q000382:microbiology*; D008231:Lymphopenia / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013921:Thrombocytopenia / Q000209:etiology
D015704:CD4 Antigens; D016207:Cytokines; D007371:Interferon-gamma