Grant: Operating Grant

In the past, we have been able to clearly demonstrate that the protozoan parasite Leishmania can affect the MO signaling leading to its dysfunctions, thus providing a secure niche where the parasite can divide and progress within its infected host. These functional inhibitions have been correlated to the activation of the host phosphotyrosine phosphatase SHP-1 conducting to signaling pathways alteration (Jak2-STAT1, NF-kB). Now, in order to have a global view on how protozoan parasites have evolved to directly or indirectly affect MO functions that favor their installment and propagation within the mammalian host, we are very keen to dissect the signaling mechanisms by which the parasite Plasmodium manipulates its host at the cellular and molecular levels. In this regard, we consider that HZ could play a pivotal role as an immunomodulator during malaria infection. On the one hand, it could contribute to inflammatory responses potentially involved in fever and anemia and, on the other hand, inhibit important MO functions (Antigen presentation) involved in the development of protective immunity. Until now, very few studies have scrutinized the signaling mechanisms involved in HZ-mediated MO modulation in vitro and in vivo. Consequently, the proposed study should permit to further reinforce the importance of HZ in the development of malaria-related pathology, and to better understand how this metabolic waste can modulate host inflammatory response conducting to specific pathologies. Results obtained from this study could provide insight into the development of new treatments to reduce fever and anemia occurring during the course of malaria infection.