NK cells and innate immunity to malaria

Innate immune response against Plasmodium falciparum (Pf), a causative agent of human malaria, is the result of several thousand years of co-evolution between the parasite and his host. An early IFN-gamma production during infection is associated with a better evolution of the disease. Natural killer (NK) cells are among the first cells in peripheral blood to produce IFN-gamma in response to Pf-infected erythrocytes (Pf-E). NK cells are found in blood, in secondary lymphoid organs as well as in peripheral non-lymphoid tissues. They participate in host innate responses that occur upon viral and intracytoplasmic bacterial infections, but also during the course of tumor development and allogeneic transplantation. These lymphocytes are not only important players of innate effector responses, but also participate in the initiation and development of adaptive immune responses. In addition, direct sensing of Pf infection by NK cells induces their production of the proinflammatory chemokine IL-8, suggesting a role for NK cells in the recruitment and the activation of other cells during malaria infection. Several other cell subsets are involved in the innate immune response to Pf. Dendritic cells, macrophages, gamma delta T cells, NKT cells are able to sense the presence of the parasite. Along this line, the presence of IL-12 is necessary to NK cell IFN-gamma production and a functional cooperation takes place between macrophages and NK cells in the context of this parasitic infection. In particular, IL-18 produced by macrophages is a key factor for this NK response. However, the molecular basis of Pf-E recognition by NK cells as well as the functional role of NK cell responses during the course of the disease remain to be adressed.