ArticlePLoS pathogens2015
Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Multicohort transcriptome analysis of whole blood identifies robust human response signatures in Plasmodium falciparum infections.Malaria journal · 2022Pooled it
- Protocol for repeated Plasmodium chabaudi infection in a murine malaria model.STAR protocols · 2026Article
- The LEF1-LAG3 axis regulates CD4Parasites & vectors · 2026Article
- Cellular and molecular interactions underlying the peripheral immune responses to blood-stage malaria infections.ImmunoHorizons · 2026Review
- TEpiNom: A computational framework integrating population data to prioritize Plasmodium falciparum T cell epitopes.Vaccine · 2026Article
- Computational Prioritization of T Cell Epitopes to Overcome HLA Restriction and Antigenic Diversity inbioRxiv : the preprint server for biology · 2025Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Differential Response and Recovery Dynamics of HSPC Populations FollowingInternational journal of molecular sciences · 2025Article
- The microbiota, the malarial parasite, and the mice-a three-sided relationship.Frontiers in microbiology · 2025Review
- RACK1 enhances STAT3 stability and promotes T follicular helper cell development and function during blood-stage Plasmodium infection in mice.PLoS pathogens · 2024Article
- ATG5-regulated CCL2/MCP-1 production in myeloid cells selectively modulates anti-malarial CD4Autophagy · 2024Article
- CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Cytokine gene polymorphisms implicated in the pathogenesis ofFrontiers in immunology · 2024Review
- Antibody-dependent immune responses elicited by blood stage-malaria infection contribute to protective immunity to the pre-erythrocytic stages.Current research in immunology · 2023Article
- Review
- Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children.Nature communications · 2022Article
- Temporally Evolving and Context-Dependent Functions of Cytokines That Regulate Murine Anti-Pathogens (Basel, Switzerland) · 2022Review
- ICOS Expression Is Required for Maintenance but Not the Formation of Germinal Centers in the Spleen in Response to Plasmodium yoelii Infection.Infection and immunity · 2022Article
- B cell-intrinsic TBK1 is essential for germinal center formation during infection and vaccination in mice.The Journal of experimental medicine · 2022Article
- The concerted change in the distribution of cell cycle phases and zone composition in germinal centers is regulated by IL-21.Nature communications · 2021Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Interleukin-21 signaling is important for germinal center B-cell responses, isotype switching and generation of memory B cells. However, a role for IL-21 in antibody-mediated protection against pathogens has not been demonstrated. Here we show that IL-21 is produced by T follicular helper cells and co-expressed with IFN-γ during an erythrocytic-stage malaria infection of Plasmodium chabaudi in mice. Mice deficient either in IL-21 or the IL-21 receptor fail to resolve the chronic phase of P. chabaudi infection and P. yoelii infection resulting in sustained high parasitemias, and are not immune to re-infection. This is associated with abrogated P. chabaudi-specific IgG responses, including memory B cells. Mixed bone marrow chimeric mice, with T cells carrying a targeted disruption of the Il21 gene, or B cells with a targeted disruption of the Il21r gene, demonstrate that IL-21 from T cells signaling through the IL-21 receptor on B cells is necessary to control chronic P. chabaudi infection. Our data uncover a mechanism by which CD4+ T cells and B cells control parasitemia during chronic erythrocytic-stage malaria through a single gene, Il21, and demonstrate the importance of this cytokine in the control of pathogens by humoral immune responses. These data are highly pertinent for designing malaria vaccines requiring long-lasting protective B-cell responses.
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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.