NITRIC OXIDE IS INVOLVED IN EARLY HOST DEFENSE AGAINST A PRIMARY INFECTION WITH BABESIA MICROTI IN MICE

Abstract

The role of nitric oxide in immune defense against primary infection with Babesia microti was investigated in the present study. Babesia microti infected C57B1 mice reach peak of parasitemia around day 14 PI. with approximately 45% PRBC and a moderate fall in hematocrit. C57B1 mice treated with the iNOS- inhibitor aminoguanidine reached a 55% PRBC peak parasitemia and the hematocrit dropped to approximately 29% PBCV. C57B1 iNOS-/- mice reached a peak parasitemia of more than 80% PRBC within 10 days Pl. and their hematocrit dropped to about 20% PBCV. The clearance of parasites from the peripheral blood and recovery of the hematocrit in aminoguanidine-treated C57B1 mice and iNOS-/-mice takes much longer than in the C57B1 wildtype control mice. During the course of infection there were marked differences in cytokine expression patterns of IFN-γ and TNF-α between C57B1 wildtype and C57B1 iNOS-/- mice. C57B1 wildtype mice treated with anti-IFN-γ mAB followed a different course of infection and survived the infection. On the other hand iNOS-/-mice treated with anti-IFN-γ mAB failed to control the rapid rise in parasitemia and died. Surviving animals of the iNOS-/- and anti-IFN-γ mAB-treated iNOS-/- groups subsequently developed sever kidney damage. These results show that NO is involved in early control of primary infection with Babesia microti, but also suggest that for the control of the acute stage of infection the effect of IFN-γ is not exclusively mediated through the induction of NO.