ArticleInfection and immunity2014
Functional roles for C5a and C5aR but not C5L2 in the pathogenesis of human and experimental cerebral malaria.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?Malaria journal · 2016Pooled it
- Immune regulation by erythroid cells: how erythroid progenitor cells and mature red blood cells shape immunity.Nature reviews. Immunology · 2026Review
- The Complement System in the Setting of Critical Illness-A Narrative Review.Biomolecules · 2026Review
- Systems approach identifies monocyte imbalance in symptomatic and asymptomatic P. vivax malaria.Molecular systems biology · 2025Article
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- Article
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Efficacy of artesunate combined with Atractylodes lancea or Prabchompoothaweep remedy extracts as adjunctive therapy for the treatment of cerebral malaria.BMC complementary medicine and therapies · 2023Article
- The Defensive Interactions of Prominent Infectious Protozoan Parasites: The Host's Complement System.Biomolecules · 2022Review
- Euterpe oleracea fruit (Açai)-enriched diet suppresses the development of experimental cerebral malaria induced by Plasmodium berghei (ANKA) infection.BMC complementary medicine and therapies · 2022Article
- Interaction Between the Complement System and Infectious Agents - A Potential Mechanistic Link to Neurodegeneration and Dementia.Frontiers in cellular neuroscience · 2021Review
- Desperately Seeking Therapies for Cerebral Malaria.Journal of immunology (Baltimore, Md. : 1950) · 2020Review
- Melatonin Prevents Brain Damage and Neurocognitive Impairment Induced byFrontiers in cellular and infection microbiology · 2020Article
- Release of endothelial activation markers in lungs of patients with malaria-associated acute respiratory distress syndrome.Malaria journal · 2019Article
- New insights into microvascular injury to inform enhanced diagnostics and therapeutics for severe malaria.Virulence · 2019Review
- Genetic analysis of cerebral malaria in the mouse model infected with Plasmodium berghei.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- T Cell Expression of C5a Receptor 2 Augments Murine Regulatory T Cell (TJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- The Rough Guide to Monocytes in Malaria Infection.Frontiers in immunology · 2018Review
- The Controversial C5a Receptor C5aR2: Its Role in Health and Disease.Journal of immunology research · 2017Review
- USP15 regulates type I interferon response and is required for pathogenesis of neuroinflammation.Nature immunology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The host immune response plays an important role in the onset and progression of cerebral malaria (CM). The complement system is an essential component of the innate immune response to malaria, and its activation generates the anaphylatoxin C5a. To test the hypothesis that C5a signaling contributes to the pathogenesis of CM, we investigated a causal role for the C5a receptors C5aR and C5L2 in a mouse model of experimental CM (ECM) induced by Plasmodium berghei ANKA infection, and using a case-control design, we examined levels of C5a in plasma samples from Ugandan children presenting with CM or uncomplicated malaria (UM). In the ECM model, C5aR(-/-) mice displayed significantly improved survival compared to their wild-type (WT) counterparts (P = 0.004), whereas C5L2(-/-) mice showed no difference in survival from WT mice. Improved survival in C5aR(-/-) mice was associated with reduced levels of the proinflammatory cytokines tumor necrosis factor (TNF) and gamma interferon (IFN-γ) and the chemokine, monocyte chemoattractant protein 1 (MCP-1) (CCL2). Furthermore, endothelial integrity was enhanced, as demonstrated by increased levels of angiopoietin-1, decreased levels of angiopoietin-2 and soluble ICAM-1, and decreased Evans blue extravasation into brain parenchyma. In the case-control study, the median levels of C5a at presentation were significantly higher in children with CM versus those in children with UM (43.7 versus 22.4 ng/ml; P < 0.001). These findings demonstrate that C5a is dysregulated in human CM and contributes to the pathogenesis of ECM via C5aR-dependent inflammation and endothelial dysfunction.
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Registered trials
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