ArticlePLoS pathogens2017
P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Regulatory T-cell Sensing of Extracellular ATP via P2RX7 Promotes Their Accumulation and Suppression and Drives Lung Tumor Growth.Cancer immunology research · 2026Article
- Host-directed therapeutic strategies against apicomplexan parasites: targeting purinergic P2 receptors.Purinergic signalling · 2026Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
- Purinergic signaling in the gut neuro-glial-immune axis: mechanisms of homeostasis, inflammation, and gastrointestinal dysfunction.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Review
- Impact of Absent in Melanoma 2 (AIM2) on Antigen-Specific CD4+ T cell Activation and Homeostasis.bioRxiv : the preprint server for biology · 2025Article
- T follicular helper cell development during malaria.Current opinion in immunology · 2025Review
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
- Targeting T-Cell Activation for Malaria Immunotherapy: Scoping Review.Pathogens (Basel, Switzerland) · 2025Article
- Leveraging adenosine triphosphate for cancer theranostics.Theranostics · 2025Review
- ATG5-regulated CCL2/MCP-1 production in myeloid cells selectively modulates anti-malarial CD4Autophagy · 2024Article
- Distinct evolution of type I glutamine synthetase in Plasmodium and its species-specific requirement.Nature communications · 2023Article
- Tissue- and temporal-specific roles of extracellular ATP on T cell metabolism and function.Immunometabolism (Cobham, Surrey) · 2023Review
- The role of extracellular ATP and P2X receptors in the pathogenesis of HIV-1.Current opinion in pharmacology · 2023Review
- Exploration of the link between gut microbiota and purinergic signalling.Purinergic signalling · 2023Review
- P2RX7 signaling drives the differentiation of Th1 cells through metabolic reprogramming for aerobic glycolysis.Frontiers in immunology · 2023Article
- Effector Memory-Expressing CD45RA (TEMRA) CD8Journal of the American Society of Nephrology : JASN · 2022Article
- Purinergic modulation of the immune response to infections.Purinergic signalling · 2022Review
- Editorial: Extracellular Nucleotides in Lymphocyte Function.Frontiers in cell and developmental biology · 2022Article
- Review
- P2RX7 at the Host-Pathogen Interface of Infectious Diseases.Microbiology and molecular biology reviews : MMBR · 2021Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. However, it is still unclear whether recognition of damage signals influences the immune response to Plasmodium infection. Adenosine triphosphate (ATP) accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. The P2X7 receptor senses extracellular ATP and induces CD4 T cell activation and death. Here we show that P2X7 receptor promotes T helper 1 (Th1) cell differentiation to the detriment of follicular T helper (Tfh) cells during blood-stage Plasmodium chabaudi malaria. The P2X7 receptor was activated in CD4 T cells following the rupture of infected erythrocytes and these cells became highly responsive to ATP during acute infection. Moreover, mice lacking the P2X7 receptor had increased susceptibility to infection, which correlated with impaired Th1 cell differentiation. Accordingly, IL-2 and IFNγ secretion, as well as T-bet expression, critically depended on P2X7 signaling in CD4 T cells. Additionally, P2X7 receptor controlled the splenic Tfh cell population in infected mice by promoting apoptotic-like cell death. Finally, the P2X7 receptor was required to generate a balanced Th1/Tfh cell population with an improved ability to transfer parasite protection to CD4-deficient mice. This study provides a new insight into malaria immunology by showing the importance of P2X7 receptor in controlling the fine-tuning between Th1 and Tfh cell differentiation during P. chabaudi infection and thus in disease outcome.
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