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.
| Original language | English |
|---|---|
| Pages (from-to) | e1004715 |
| Journal | PLOS PATHOGENS |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2015 |
Keywords
- Animals
- B-Lymphocytes/immunology
- Cell Communication/immunology
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Flow Cytometry
- Immunity, Humoral/immunology
- Interleukins/immunology
- Malaria/immunology
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Plasmodium chabaudi/immunology
- Plasmodium yoelii/immunology
- Real-Time Polymerase Chain Reaction
- Signal Transduction
- T-Lymphocytes/immunology