Trial reportPLoS pathogens2014
Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection.
Trial report in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 114 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- The role of CD36 in immune function: bridging innate and adaptive responses.Frontiers in immunology · 2026Pooled it
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Article
- Macrophage metabolic exhaustion and PANoptotic cell death drive chronic tissue inflammation in rheumatoid arthritis.Immunity · 2026Article
- Conservation of NLRP3 Inflammasome Pathway in Monotremes and Large-Scale Restructuring of the Caspase-1 Gene Cluster Region in Mammals.Journal of molecular evolution · 2026Article
- Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance tobioRxiv : the preprint server for biology · 2026Article
- Transcriptome profiling of peripheral blood mononuclear cells from highly susceptible adult cattle infected with a virulent strain of Babesia bovis.Parasites & vectors · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Emerging Role of Splenic Macrophage in Malaria Pathogenesis and Immunity.Immunity, inflammation and disease · 2025Review
- Immune regulation of host energy metabolism and periodicity of malaria parasites.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- NOD-like receptors in fish: evolution, structure, immune signaling, and targeting for aquaculture vaccine adjuvants.Frontiers in immunology · 2025Review
- Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.Immunological reviews · 2025Review
- Inflammasomes and their role in PANoptosomes.Current opinion in immunology · 2024Review
- The role of NLRP3 and NLRP12 inflammasomes in glioblastoma.Genes and immunity · 2024Review
- Role of inflammasomes in Toxoplasma and Plasmodium infections.Parasites & vectors · 2024Review
- NLRC5 senses NADCell · 2024Article
- Molecular regulation of NLRP3 inflammasome activation during parasitic infection.Bioscience reports · 2024Review
- The NLR family of innate immune and cell death sensors.Immunity · 2024Review
- Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cells.Cell metabolism · 2024Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1β. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-γ-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1β expression required a second stimulation with LPS and was also dependent on IFN-γ-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1β upon a second microbial stimulus, and became hypersensitive to septic shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial-induced lethality in rodents. Similar to mice, we observed a significantly increased frequency of circulating CD14(+)CD16(-)Caspase-1(+) and CD14(dim)CD16(+)Caspase-1(+) monocytes in peripheral blood mononuclear cells from febrile malaria patients. These cells readily produced large amounts of IL-1β after stimulation with LPS. Furthermore, we observed the presence of inflammasome complexes in monocytes from malaria patients containing either NLRP3 or NLRP12 pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malaria.
Indexed as
Identifiers
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.