Human Vγ9Vδ2T Lymphocytes in the Immune Response to P. falciparum Infection

Malaria is an infectious disease caused by the protozoan parasite Plasmodium sp, the most lethal being Plasmodium falciparum. Clinical malaria is associated with the asexual replication cycle of Plasmodium parasites inside the red blood cells (RBCs) and a dysregulated immune response. Although the mechanisms of immune responses to blood-or liver-stage parasites have been extensively studied, this has not led to satisfactory leads for vaccine design. Among innate immune cells responding to infection are the non-conventional gamma-delta T-cells. The V gamma 9V delta 2 T-cell subset, found only in primates, is activated in response to non-peptidic phosphoantigens produced by stressed mammalian cells or by microorganisms such as Mycobacteria, E. coli, and Plasmodium. The potential protective role of V gamma 9V delta 2 T-cells against infections and cancer progression is of current research interest. V gamma 9V delta 2 T-cells have been shown to play a role in the early control of P. falciparum parasitemia and to influence malaria adaptive immunity via cytokine release and antigen presentation. They are activated and expanded during a primary P. falciparum infection in response to malaria phosphoantigens and their activity is modulated upon subsequent infections. Here, we review the wide range of functions by which V gamma 9V delta 2 T-cells could both contribute to and protect from malaria pathology, with a particular focus on their ability to induce both innate and adaptive responses. We discuss how the multifunctional roles of these T-cells could open new perspectives on gamma-delta T-cell-based interventions to prevent or cure malaria.