Mechanisms of immunity to Ehrlichia muris: a model of monocytotropic ehrlichiosis.
Ehrlichia species can cause life-threatening infections or chronic persistent infections. Mechanisms of protective immunity were examined in an Ehrlichia muris mouse model of monocytotropic ehrlichiosis. C57BL/6 mice possessed strong genetic resistance to E. muris of an undetermined mechanism. CD8 T lymphocytes were particularly important, as revealed by 81% fatalities for E. muris-infected, major histocompatibility complex class I gene knockout mice compared with no deaths for wild-type C3H mice. Moreover, 80% of C3H mice depleted of CD8 and CD4 cells died of E. muris infection compared with only 44% of CD4 cell-depleted mice. CD8 T lymphocytes were demonstrated for the first time in an Ehrlichia infection to exhibit cytotoxic T-lymphocyte activity against Ehrlichia-infected target cells. Both gamma interferon and tumor necrosis factor were shown to play synergistic roles in protective immunity in vivo for the first time, as demonstrated by 75% fatalities when both cytokines were neutralized compared with minimal mortality when they were depleted separately. Passive transfer of antibodies, but not Fab fragments, to E. muris protected C3H/SCID mice against lethal infection. The mechanism of increased susceptibility (22% lethality) of C57BL/6 major histocompatibility complex class II gene knockout mice and CD4 cell-depleted C3H mice (i.e., through a gamma interferon or antibody mechanism), as well as the more important role of CD8 T lymphocytes (in the form of cytotoxic T-lymphocyte activity and/or gamma interferon production), remains to be elucidated. Protective immunity against monocytotropic E. muris is mediated by a combination of CD8 and CD4 T lymphocytes, gamma interferon, tumor necrosis factor alpha, and antibodies.
Feng
Hui-Min
HM
Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Walker
David H
DH
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000502:physiology; D004195:Disease Models, Animal; D004536:Ehrlichia / Q000276:immunology*; D018469:Ehrlichia chaffeensis; D016873:Ehrlichiosis / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000907:Antibodies, Bacterial; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003165:Complement System Proteins