Hernández-Castañeda, Maria Andrea Happ, Katharina Cattalani, Filippo Wallimann, Alexandra Blanchard, Marianne Fellay, Isabelle Scolari, Brigitte Lannes, Nils Mbagwu, Smart Ikechukwu Fellay, Benoît Filgueira, Luis Mantel, Pierre-Yves Walch, Michael 2020-04-01 Plasmodium spp., the causative agent of malaria, have a complex life cycle. The exponential growth of the parasites during the blood stage is responsible for almost all malaria-associated morbidity and mortality. Therefore, tight immune control of the intraerythrocytic replication of the parasite is essential to prevent clinical malaria. Despite evidence that the particular lymphocyte subset of γδ T cells contributes to protective immunity during the blood stage in naive hosts, their precise inhibitory mechanisms remain unclear. Using human PBMCs, we confirmed in this study that γδ T cells specifically and massively expanded upon activation with Plasmodium falciparum culture supernatant. We also demonstrate that these activated cells gain cytolytic potential by upregulating cytotoxic effector proteins and IFN-γ. The killer cells bound to infected RBCs and killed intracellular P. falciparum via the transfer of the granzymes, which was mediated by granulysin in a stage-specific manner. Several vital plasmodial proteins were efficiently destroyed by granzyme B, suggesting proteolytic degradation of these proteins as essential in the lymphocyte-mediated death pathway. Overall, these data establish a granzyme- and granulysin-mediated innate immune mechanism exerted by γδ T cells to kill late-stage blood-residing P. falciparum. application/pdf https://folia.unifr.ch/global/documents/308491 https://folia.unifr.ch/documents/308491/files/fill_gtc.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1900725 info:eu-repo/semantics/openAccess License undefined The Journal of Immunology. - 2020, vol. 204, no. 7, p. 1798–1809 info:eu-repo/classification/udc/57 γδ T cells kill Plasmodium falciparum in a granzyme- and granulysin-dependent mechanism during the late blood stage http://purl.org/coar/resource_type/c_6501