γδ T Cells Kill Plasmodium falciparum in a Granzyme- and Granulysin-Dependent Mechanism during the Late Blood Stage.
Maria Andrea Hernández-CastañedaKatharina HappFilippo CattalaniAlexandra WallimannMarianne BlanchardIsabelle FellayBrigitte ScolariNils LannesSmart MbagwuBenoît FellayLuis FilgueiraPierre-Yves MantelMichael WalchPublished in: Journal of immunology (Baltimore, Md. : 1950) (2020)
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.
Keyphrases
- plasmodium falciparum
- induced apoptosis
- cell cycle arrest
- endothelial cells
- dendritic cells
- innate immune
- life cycle
- oxidative stress
- blood brain barrier
- peripheral blood
- artificial intelligence
- big data
- risk assessment
- endoplasmic reticulum stress
- cell death
- electronic health record
- anti inflammatory
- deep learning
- human health
- cell proliferation