Stromal cell-derived factor-1 production by spleen cells is affected by nitric oxide in protective immunity against blood-stage Plasmodium chabaudi CR in C57BL/6j mice.

Abstract Malaria, a major endemic tropical disease, is caused by the infection of blood cells by Plasmodium protozoa. Most patients control their parasitemia by a not fully understood spleen-dependent mechanism. SDF-1α is a chemokine produced by stromal cells such as reticular spleen cells. Nitric oxide (NO) has several immune functions, including killing of intracellular pathogens and its function in malaria is debated. We have previously shown that SDF-1α production peaks during the ascending parasitemia in Plasmodium chabaudi infection and its supplementation in lethal models could reduce the parasitemia. In the present study, we analyzed SDF-1 production by spleen cells as related to NO metabolism in the P. chabaudi rodent malaria model using IFN-γ; TNFR and iNOS-knockout mice or iNOS-blocked, l -NAME- or aminoguanidine-treated mice. Parasitemia and production of SDF-1α and SDF-1β were determined by RT-PCR. In vitro NO production by spleen adherent cells was also tested. The data showed that parasitemia was less intense in both iNOS −/− or NO-inhibited mice than in controls, with increased and long-lasting production of SDF-1α mRNA. In the absence of cytokines involved in the final regulation of NO production by effector cells, as is the case for TNFR −/− and GKO mice, the infection progressed in an uncontrolled manner regardless of SDF-1α production, suggesting that these cytokines must be involved in the control of parasitemia after the SDF-1α dependent process. The SDF-1β isoform was constitutive in all experiments, with elevated levels only clearly seen in TNFR −/− mice. We conclude that SDF-1 is involved in the promotion of parasitemia control in malaria, and excessive NO could affect its production.