Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria

PLoS Pathogens
Damian Perez-MazliahJ Langhorne

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 im...Continue Reading

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Citations

Feb 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Nicolas F VillarinoNathan W Schmidt
Dec 15, 2015·FEMS Microbiology Reviews·Katrien DeroostPhilippe E Van den Steen
Mar 3, 2018·Immunology and Cell Biology·Beatriz GarcillánFabienne Mackay
Nov 6, 2018·ELife·Damián Pérez-MazliahJean Langhorne
Jan 9, 2016·Parasitology·Victoria Ryg-CornejoDiana S Hansen
Nov 22, 2019·The Journal of Experimental Medicine·E Nicole Arroyo, Marion Pepper
Apr 4, 2019·Nature Reviews. Immunology·Samarchith P KurupJohn T Harty
Jan 9, 2019·Frontiers in Immunology·Eduardo L V SilveiraIrene S Soares
Nov 17, 2019·Immunological Reviews·Damián Pérez-MazliahJean Langhorne
Nov 1, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel Fernandez-RuizWilliam R Heath
Jan 13, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kylie R JamesAshraful Haque
Apr 20, 2019·Frontiers in Immunology·Ann Ly, Diana S Hansen
Jan 12, 2019·Frontiers in Immunology·Rebecca FaleiroMichelle Wykes
Dec 24, 2019·Frontiers in Cellular and Infection Microbiology·Shahram Solaymani-MohammadiSteven M Singer
Jul 28, 2017·Parasite Immunology·I SebinaA Haque
Dec 7, 2017·Immunology·Temitope W Ademolue, Gordon A Awandare
Jan 20, 2021·Journal of Leukocyte Biology·Debopam Ghosh, Jason S Stumhofer
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Dec 29, 2020·Frontiers in Cellular and Infection Microbiology·Chunmei CaiXiao Yu
Apr 2, 2021·Probiotics and Antimicrobial Proteins·Timothy BamgboseJosé de la Fuente

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Methods Mentioned

BETA
flow cytometry
ELISA
PCR
PMA
ELISAs
Flow cytometry gating

Software Mentioned

FlowJo
ELDA
GraphPad
Prism
Tree Star

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