Role of T cells and cytokines in fatal and resolving experimental babesiosis: Protection in TNFRp55(-/-) mice infected with the human Babesia WA1 parasite

We characterized the cytokine response and T-cell requirements of mice infe cted with the intraerythrocytic parasites Babesia microti and WA1. WA1 infe ctions were fatal, whereas B. microti infections were resolved. We measured production of tumor necrosis factor (TNF)-alpha, interferon-gamma, interle ukin (IL)-10, and IL-4 by splenic CD4(+), CD8(+), and gamma delta(+) T cell s using how cytometry. WA1 inoculation stimulated TNF-alpha production, whe reas resolving B. microti infections were characterized by increased IL-10 and IL-4. The role of TNF-alpha in WA1 infections was further investigated by inoculating TNFRp55(-/-) mice with a lethal dose of WA1. A survival rate of 90% in the TNFRp55(-/-) mice indicated that a disruption in the TNF-alp ha pathway abrogated the pathologic mechanism of WA1. Inoculation of WA1 in to CD4(-/-) and CD8(-/-) mice resulted in survival rates of 60% and 78%, re spectively, whereas WA1 infection in gamma delta(-/-) and control mice was fatal. These results suggest that CD8(+) T cells may contribute to the WA1- associated disease. Babesia-infected CD4(-/-) mice experienced a longer dur ation of parasitemia, indicating that CD4(+) T cells participate in parasit e elimination. These studies demonstrate differences in immune responses du ring fatal or resolving Babesia infections, and they identify TNF-alpha as an important mediator of the WA1-associated pathogenesis.