γδ T cells kill Plasmodium falciparum in a granzyme- and granulysin-dependent mechanism during the late blood stage

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

doi:10.4049/jimmunol.1900725

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Journal article

γδ T cells kill Plasmodium falciparum in a granzyme- and granulysin-dependent mechanism during the late blood stage

Hernández-Castañeda, Maria Andrea Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Happ, Katharina Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Cattalani, Filippo Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Wallimann, Alexandra Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Blanchard, Marianne Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Fellay, Isabelle Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Scolari, Brigitte Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Lannes, Nils Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Mbagwu, Smart Ikechukwu Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Fellay, Benoît Cantonal Hospital of Fribourg, 1752 Villars-sur-Glâne, Switzerland
Filgueira, Luis Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Mantel, Pierre-Yves Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Walch, Michael Anatomy Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland

01.04.2020

Published in:

The Journal of Immunology. - 2020, vol. 204, no. 7, p. 1798–1809

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language