The IL-33/ST2 Pathway in Cerebral Malaria

Abstract

Interleukin-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.

Unravelling mysteries at the perivascular space: a new rationale for cerebral malaria pathogenesis

“…Over the years, a variety of cytokines and chemokines have been identified in CM pathogenesis, often acting in cascades. The role of CD4 + and CD8 + T cells in their overproduction, including IL-33, has recently been assessed [ 22 ].…”

Regulatory Functions of Hypoxia in Host–Parasite Interactions: A Focus on Enteric, Tissue, and Blood Protozoa

“…IL-33 prevents development of cerebral malaria (CM); however, the IL-33/ST2 pathway in mice lessens the pathogenicity of experimental cerebral malaria [ 295 , 296 ]. Ultimately, studies in the field have exemplified how IL-33 can either reduce the inflammatory response or exacerbate it depending on the cells it acts on and the location in the body [ 297 ]. Research is now warranted to characterize how this response interacts with hypoxia during infection.…”

Molecular Research on Plasmodium Infection and Immunity

“…The balance between pro-and antiinflammatory cytokine responses plays a critical role in the outcome of Plasmodium infection [11]. Here, the production of TGF-b and of IL-9 in patients with distinct malaria clinical presentations is analysed by Ndoricyimpaye et al [12], and the involvement of the IL-33/ST2 pathway in cerebral malaria is reviewed by Glineur et al [13]. Moreover, neutrophils might also play a role in the development of cerebral malaria, as analysed in a mouse model by Freire-Antunes at al.…”