Disruption of IL-21 Signaling Affects T Cell-B Cell Interactions and Abrogates Protective Humoral Immunity to Malaria

PLoS Pathogens

Sarah McLaughlin¹  Garikai Kushinga¹  Ana Paula Freitas do Rosário¹  Jan Sodenkamp¹  Dorothy Hui Lin Ng¹  Béatris Mastelic-Gavillet¹  Jean Langhorne¹  Damián Pérez-Mazliah¹ 

[1] Division of Parasitology, MRC National Institute for Medical Research (NIMR), London, United Kingdom

关键词: Parasitic diseases;    B cells;    T cells;    Spleen;    Parasitemia;    Immune response;    Cell staining;    Infectious disease immunology;   

DOI  :  10.1371/journal.ppat.1004715

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY