Pérez-Mazliah, Damián orcid.org/0000-0002-2156-2585, Nguyen, Minh Phuong, Hosking, Caroline et al. (5 more authors) (2017) Follicular Helper T Cells are Essential for the Elimination of Plasmodium Infection. EBioMedicine. pp. 216-230. ISSN 2352-3964
Abstract
CD4+ follicular helper T (Tfh) cells have been shown to be critical for the activation of germinal center (GC) B-cell responses. Similar to other infections, Plasmodium infection activates both GC as well as non-GC B cell responses. Here, we sought to explore whether Tfh cells and GC B cells are required to eliminate a Plasmodium infection. A CD4 T cell-targeted deletion of the gene that encodes Bcl6, the master transcription factor for the Tfh program, resulted in complete disruption of the Tfh response to Plasmodium chabaudi in C57BL/6 mice and consequent disruption of GC responses and IgG responses and the inability to eliminate the otherwise self-resolving chronic P. chabaudi infection. On the other hand, and contrary to previous observations in immunization and viral infection models, Signaling Lymphocyte Activation Molecule (SLAM)-Associated Protein (SAP)-deficient mice were able to activate Tfh cells, GC B cells, and IgG responses to the parasite. This study demonstrates the critical role for Tfh cells in controlling this systemic infection, and highlights differences in the signals required to activate GC B cell responses to this complex parasite compared with those of protein immunizations and viral infections. Therefore, these data are highly pertinent for designing malaria vaccines able to activate broadly protective B-cell responses.
Metadata
Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved. |
Keywords: | Animals, CD4-Positive T-Lymphocytes/immunology, Cell Differentiation, Dendritic Cells, Follicular/immunology, Gene Deletion, Immunoglobulin G/metabolism, Lymphocyte Activation, Malaria/genetics, Mice, Mice, Inbred C57BL, Plasmodium chabaudi/immunology, Proto-Oncogene Proteins c-bcl-6/genetics, T-Lymphocytes, Helper-Inducer |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 15 Oct 2019 10:50 |
Last Modified: | 06 Dec 2023 13:22 |
Published Version: | https://doi.org/10.1016/j.ebiom.2017.08.030 |
Status: | Published |
Refereed: | Yes |
Identification Number: | https://doi.org/10.1016/j.ebiom.2017.08.030 |
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