ArticleProceedings of the National Academy of Sciences of the United States of America2014
Strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Elevations in D-dimer levels in patients with Plasmodium infections: a systematic review and meta-analysis.Scientific reports · 2025Pooled it
- Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection.Nature immunology · 2026Article
- Temporal multi-tissue profiling reveals metabolites linked to immune response and malaria parasitemia control.iScience · 2026Article
- Palmitoylation of TBK1 enhances the type I interferon signaling and strengthens anti-malarial immunity in mice.Nature communications · 2025Article
- Dual nature of type I interferon responses and feedback regulations by SOCS1 dictate malaria mortality.Journal of advanced research · 2025Article
- The intensity of the transcriptional response varies across infection with distinct viral strains in an insect host.BMC genomics · 2025Article
- Bulk and single-cell transcriptome profiling reveals the dynamic immune response in granulomatous amebic encephalitis caused byFrontiers in immunology · 2025Article
- Role of inflammasomes in Toxoplasma and Plasmodium infections.Parasites & vectors · 2024Review
- Comparative genomics of Plasmodium yoelii nigeriensis N67 and N67C: genome-wide polymorphisms, differential gene expression, and drug resistance.BMC genomics · 2024Article
- NAD activates olfactory receptor 1386 to regulate type I interferon responses inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Role of TAM Receptors in Antimalarial Humoral Immune Response.Pathogens (Basel, Switzerland) · 2024Review
- Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cells.Cell metabolism · 2024Article
- Article
- Malaria Genomics, Vaccine Development, and Microbiome.Pathogens (Basel, Switzerland) · 2023Review
- Function and regulation of cGAS-STING signaling in infectious diseases.Frontiers in immunology · 2023Review
- Genetic mapping of determinants in drug resistance, virulence, disease susceptibility, and interaction of host-rodent malaria parasites.Parasitology international · 2022Review
- Friend or foe: RIG- I like receptors and diseases.Autoimmunity reviews · 2022Review
- Review
- Activation of cGAS-STING by Lethal Malaria N67C Dictates Immunity and Mortality through Induction of CD11bAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- CD4Malaria journal · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors, and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within RBCs, thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi-based gene knockdown and KO mice, we demonstrated that a strong type I IFN (IFN-I) response triggered by RNA polymerase III and melanoma differentiation-associated protein 5, not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine on infected RBCs might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis.
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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.