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Follicular helper T cells are essential for the elimination of Plasmodium infection
journal contributionposted on 2020-10-09, 06:49 authored by Damián Pérez-Mazliah, Minh Phuong Nguyen, Caroline Hosking, Sarah McLaughlin, Matthew D Lewis, Irene Tumwine, Prisca Levy, Jean Langhorne
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.
Follicular helper T (Tfh) cellsGC B cellsPlasmodiumSignaling Lymphocyte Activation Molecule (SLAM)-Associated Protein (SAP)Vector transmissionAnimalsCD4-Positive T-LymphocytesCell DifferentiationDendritic Cells, FollicularGene DeletionImmunoglobulin GLymphocyte ActivationMalariaMiceMice, Inbred C57BLPlasmodium chabaudiProto-Oncogene Proteins c-bcl-6T-Lymphocytes, Helper-InducerLanghorne FC001101BRF-ackFC-ackHP-ack