ArticleThe Journal of biological chemistry2005
Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 1 of them a synthesis that pooled it.
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Who cites it
255 citing papers in PubMed, 1 synthesis or guideline pooled it, 481 citations in OpenAlex.
- Pooled it
- Exposure-dependent control of malaria-induced inflammation in children.PLoS pathogens · 2014Trial
- Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection.PLoS pathogens · 2014Trial
- Innate immune sensing of Plasmodium sporozoite cell traversal drives protective T cell responses.Nature microbiology · 2026Article
- Cross-species TNF-α signaling in mosquitoes promotes malaria transmission.EMBO reports · 2026Article
- Cellular nucleic acid-binding protein (CNBP) dependent cytokine programming shapes host defense againstbioRxiv : the preprint server for biology · 2026Article
- Latent cytomegalovirus disrupts innate NK cell responses to P. falciparum and impairs parasite control in first infection in adults.PLoS pathogens · 2026Article
- Anti-GPI scFv as a Promising Tool for Intervention Against Cerebral Malaria in Mice.International journal of molecular sciences · 2026Article
- Mapping the expression of endothelial adhesion receptors for Plasmodium falciparum-infected erythrocytes in fatal cerebral malaria in Malawian children.Journal of neuropathology and experimental neurology · 2025Article
- New Evidence of TLR4 and TLR9 Variants Influencing Parasitaemia and Symptoms of Plasmodium vivax Infection.International journal of immunogenetics · 2025Article
- Emerging Role of Splenic Macrophage in Malaria Pathogenesis and Immunity.Immunity, inflammation and disease · 2025Review
- Immunoinformatics-Based Multi-Epitope Vaccine Design AgainstHealth science reports · 2025Article
- Age is an intrinsic driver of inflammatory responses to malaria.Nature communications · 2025Article
- Hexosamine biosynthesis disruption impairs GPI production and arrests Plasmodium falciparum growth at schizont stages.PLoS pathogens · 2025Article
- Immune regulation of host energy metabolism and periodicity of malaria parasites.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Current Developments in Malaria Vaccination: A Concise Review on Implementation, Challenges, and Future Directions.Clinical pharmacology : advances and applications · 2025Review
- The GPI sidechain ofmBio · 2024Article
- Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism.Pathogens (Basel, Switzerland) · 2024Article
- Surface proteome of plasma extracellular vesicles as mechanistic and clinical biomarkers for malaria.Infection · 2023Article
- The characterization of toll-like receptor repertoire inEcology and evolution · 2023Article
195 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum have been proposed to be the major factors that contribute to malaria pathogenesis through their ability to induce proinflammatory responses. In this study we identified the receptors for P. falciparum GPI-induced cell signaling that leads to proinflammatory responses and studied the GPI structure-activity relationship. The data show that GPI signaling is mediated mainly through recognition by TLR2 and to a lesser extent by TLR4. The activity of sn-2-lyso-GPIs is comparable with that of the intact GPIs, whereas the activity of Man(3)-GPIs is about 80% that of the intact GPIs. The GPIs with three (intact GPIs and Man(3)-GPIs) and two fatty acids (sn-2-lyso-GPIs) appear to differ considerably in the requirement of the auxiliary receptor, TLR1 or TLR6, for recognition by TLR2. The former are preferentially recognized by TLR2/TLR1, whereas the latter are favored by TLR2/TLR6. However, the signaling pathways initiated by all three GPI types are similar, involving the MyD88-dependent activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 and NF-kappaB-signaling pathways. The signaling molecules of these pathways differentially contribute to the production of various cytokines and nitric oxide (Zhu, J., Krishnegowda, G., and Gowda, D. C. (2004) J. Biol. Chem. 280, 8617-8627). Our data also show that GPIs are degraded by the macrophage surface phospholipases predominantly into inactive species, indicating that the host can regulate GPI activity at least in part by this mechanism. These results imply that macrophage surface phospholipases play important roles in the GPI-induced innate immune responses and malaria pathogenesis.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.