Malaria infection protects from lupus nephritis at a stage beyond immune complex-induced glomerular inflammation

Abstract A protective role of malaria infection in SLE was proposed to explain the relatively low prevalence of SLE in West Africa compared to populations of similar genetic background living in the West. Various reports showed an increase of autoantibodies in plasma of West African populations, suggesting that parasite infections were inducing systemic autoreactivity while protecting from tissue pathology. Our own studies from a large longitudinal study in a malaria endemic region confirm the high penetrance of elevated titers of anti-nuclear antibodies in plasma of Plasmodium PCR-positive individuals. In mouse models of malaria, murine Plasmodium infection increases systemic autoreactivity but does not trigger any type of immune-complex induced inflammatory disease. To further investigate the mechanism of kidney protection by Plasmodium, we set up experiments using a malaria parasite in the well characterized SLE mouse model FcγRIIb[KO]. This model system allowed for evaluation of the effect of malaria on autoantibodies, systemic vasculitis and kidney specific pathology, while also assessing the role of parasite-mediated bone marrow alterations, or parasite-produced hemozoin. We found that infection with Plasmodium protects SLE by modifying bone marrow cells and impairing leukocyte infiltration in the kidney, without altering systemic autoimmunity, vasculitis, all independent of the expression of hemozoin. Our results point to a protection of late-stage kidney disease by malaria that targets a step beyond immune complex deposition, hypoxia or innate responses and release of cytokines (IFN, TNF, IL1).