Protection from neuroinflammation by blood stage malaria is due to a RNA virus A. Hassan1, M. Wlodarczyk1, A. Salvioni1, E. Bassot1, M. Benamar1, S. Kassem1, A. Saoudi1, N. Blanchard1* 1Centre de Physiopathologie Toulouse-Purpan (CPTP), INSERM, CNRS, Université de Toulouse, France *Corresponding Author
Exposure to infectious agents, including parasites, bacteria and viruses, is likely to influence the immune status of a host at any life stage, with detrimental or beneficial consequences on the development of inflammatory diseases. Malaria infection is caused by parasites of the Plasmodium genus. Malaria has been suggested to play a protective role in human Multiple Sclerosis as well in Experimental Autoimmune Encephalomyelitis (EAE). In addition, the clinical evolution of malaria itself, such as the onset of a deadly neuroinflammatory condition called Cerebral Malaria, is influenced by infection with concurrent Plasmodium species. Yet the underlying protective mechanisms are largely unknown. Here we show that transfusion of blood parasitized by the rodent Plasmodium berghei K173 (Pb K173) malaria strain confers full protection against Pb ANKA-induced Experimental Cerebral Malaria (ECM) and against MOG-induced EAE. Protection against ECM correlated with a strong decrease in the development of CD4 Th1 cells. Protection against EAE was accompanied by blunted differentiation of MOG-specific Th1, Th17 and ThGM-CSF CD4 T cells. The fact that this immune modulation was associated with an IFN-I signature and transmissible to new mice independently from the parasites suggested the presence of a virus. We indeed found an RNA virus called Lactate Dehydrogenase-elevating Virus (LDV) in Pb K173 stabilates as well as in other stocks of the community. LDV leads to chronic asymptomatic infection with high persisting circulating viremia. We demonstrated that infection with LDV entirely recapitulates the modulatory effects of Pb K173. Experiments are underway to elucidate the molecular pathways through which LDV infection abrogates the encephalitogenic differentiation of autoreactive CD4 T cells. Since LDV is present in several Plasmodium stocks, we expect these findings to have dramatic consequences for the malaria research community. This study may also reveal new pathways by which a persisting viral infection dampens CNS autoimmunity, potentially suggesting novel therapeutic approaches to treat MS.
Funding: ARSEP, Idex Toulouse
Credits: None available.
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