Stimulation of innate immune responses by malarial glycosylphosphatidylinositol via pattern recognition receptors.
The glycosylphosphatidylinositol (GPI) anchor of Plasmodium falciparum is thought to function as a critical toxin that contributes to severe malarial pathogenesis by eliciting the production of proinflammatory responses by the innate immune system of mammalian hosts. Analysis of the fine structure of P. falciparum GPI suggests a requirement for the presence of both core glycan and lipid moieties in the recognition and signalling of parasite glycolipids by host immune cells. It has been demonstrated that GPI anchors of various parasitic protozoa can mediate cellular immune responses via members of the Toll-like family of pattern recognition receptors (TLRs). Recent studies indicate that GPI anchors of P. falciparum and other protozoa are preferentially recognized by TLR-2, involving the MyD88-dependent activation of specific signalling pathways that mediate the production of proinflammatory cytokines and nitric oxide from host macrophages in vitro. However, the contribution of malaria GPI toxin to severe disease syndromes and the role of specific TLRs or other pattern recognition receptors in innate immunity in vivo is only just beginning to be characterized. A better understanding of the molecular mechanisms underlying severe malarial pathogenesis may yet lead to substantial new insights with important implications for the development of novel therapeutics for malaria treatment.
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The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
De Veer
M J
MJ
Schofield
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D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000502:physiology*; D007113:Immunity, Innate; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D010961:Plasmodium / Q000276:immunology* / Q000472:pathogenicity*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D051193:Toll-Like Receptors / Q000378:metabolism
D017261:Glycosylphosphatidylinositols; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D048049:Extracellular Signal-Regulated MAP Kinases