Nitric oxide is neither necessary nor sufficient for resolution of Plasmodium chabaudi malaria in mice

Malaria is a life-threatening re-emerging disease, yet it is still not clea r how bloodstage malarial parasites are killed. Nitric oxide (NO), which ha s potent anti-microbial activity, may represent an important killing mechan ism. The production of NO during descending Plasmodium chabaudi parasitemia , a period when parasites are killed by the immune response, supports this concept. However, NOS2(0/0) and NOS3(0/0) mice as well as mice treated with NO synthase 2 (NOS2) inhibitors do not develop exacerbated malaria, indica ting that NO production is not necessary for the suppression of P, chabaudi parasitemia, It is possible due to the plasticity in the immune response d uring malaria that Ah-mediated immunity is enhanced in the absence of NO, t hereby explaining the lack of exacerbated malaria in NOS-deficient mice eve n though NO may function in protection. However, NOS2- and B cell-deficient mice, which cannot use Ah-mediated immunity, suppress their parasitemia wi th a similar time course as B cell-deficient controls. C57BL/6 mice treated with Propionibacterium acnes to elicit high levels of macrophage-derived N O have a similar time course of P, chabaudi parasitemia as P, acnes-treated NOS2(0/0) mice, which do not produce NO; this indicates that NO is not suf ficient for parasite killing. Collectively, these results indicate that NO is not necessary or sufficient to resolve P, chabaudi malaria.