The IL-33/ST2 Pathway in Cerebral Malaria

International audienceInterleukin-33 (IL-33) is an immunomodulatory cytokine which plays critical roles in tissue function and immune-mediated diseases. IL-33 is abundant within the brain and spinal cord tissues where it acts as a key cytokine to coordinate the exchange between the immune and central nervous system (CNS). In this review, we report the recent advances to our knowledge regarding the role of IL-33 and of its receptor ST2 in cerebral malaria, and in particular, we highlight the pivotal role that IL-33/ST2 signaling pathway could play in brain and cerebrospinal barriers permeability. IL-33 serum levels are significantly higher in children with severe Plasmodium falciparum malaria than children without complications or noninfected children. IL-33 levels are correlated with parasite load and strongly decrease with parasite clearance. We postulate that sequestration of infected erythrocytes or merozoites liberation from schizonts could amplify IL-33 production in endothelial cells, contributing either to malaria pathogenesis or recovery.</jats:p

Autophagy Pathways in the Genesis of Plasmodium-Derived Microvesicles: A Double-Edged Sword?

International audienceMalaria, caused by Plasmodium species (spp.), is a deadly parasitic disease that results in approximately 400,000 deaths per year globally. Autophagy pathways play a fundamental role in the developmental stages of the parasite within the mammalian host. They are also involved in the production of Plasmodium-derived extracellular vesicles (EVs), which play an important role in the infection process, either by providing nutrients for parasite growth or by contributing to the immunopathophysiology of the disease. For example, during the hepatic stage, Plasmodium-derived EVs contribute to parasite virulence by modulating the host immune response. EVs help in evading the different autophagy mechanisms deployed by the host for parasite clearance. During cerebral malaria, on the other hand, parasite-derived EVs promote an astrocyte-mediated inflammatory response, through the induction of a non-conventional host autophagy pathway. In this review, we will discuss the cross-talk between Plasmodium-derived microvesicles and autophagy, and how it influences the outcome of infection

Role of astrocyte senescence induced by Plasmodium in the pathogenesis of Cerebral Malaria

International audienceCerebral malaria (CM) is a fatal neurological syndrom due to Plasmodium (P.) falciparum infection, which kills 405,000 people annually(1). A central event involved in the pathogenesis of CM is the sequestration of infected red blood cells in the brain capillaries and the inflammatory response of activated glial cells (2). However, molecular mechanisms involved in the induction of the pro-inflammatory response of glial cells during CM remains unknown. In this study, we have examined if the senescence of glial cells induced by P. berghei ANKA infection participates in the neuroinflammatory response associated to CM

Role of astrocyte senescence induced by Plasmodium in the pathogenesis of Cerebral Malaria

International audienceCerebral malaria (CM) is a fatal neurological syndrom due to Plasmodium (P.) falciparum infection, which kills 405,000 people annually(1). A central event involved in the pathogenesis of CM is the sequestration of infected red blood cells in the brain capillaries and the inflammatory response of activated glial cells (2). However, molecular mechanisms involved in the induction of the pro-inflammatory response of glial cells during CM remains unknown. In this study, we have examined if the senescence of glial cells induced by P. berghei ANKA infection participates in the neuroinflammatory response associated to CM

A noncanonical autophagy is involved in the transfer of Plasmodium -microvesicles to astrocytes

International audienc