Grant: Operating Grant - Priority Announcement: Infection and Immunity (Bridge Funding)

Various type of diseases can affect host physiology by targeting for instance liver of human. In this regard, heme-based inorganic cristal (hemozoin; HZ) generated during malaria infection could concur to the development of hepatosplenomegaly. In order to better understand how HZ have evolved to directly or indirectly influence macrophage inflammatory responses and the development of liver enlargment, we are very keen to dissect the signaling mechanisms by which HZ 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 macrophage functions (Antigen presentation) involved in the development of protective immunity. Until now, very few studies have scrutinized the signaling mechanisms involved in HZ-mediated macrophage 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 such as hepatosplenomegaly, 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, anemia and abnormal liver physiology occurring during the course of malaria infection.