Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Abstract

The importance of the interaction between natural killer (NK) cells and dendritic cells (DCs) in the expansion of antiviral and antitumor immune responses is well-documented; however, limited information on DC-NK cell interaction during parasitic infections is available. Given that some Leishmania parasites are known to prevent or suppress DC activation, we developed a DC-NK cell coculture system to examine the role of NK cells in modulating the functions of Leishmania-infected DCs. We found that the addition of freshly isolated, resting NK cells significantly promoted the activation of DCs that were preinfected with Leishmania amazonensis promastigotes and that these activated DCs, in turn, stimulated NK cell activation mostly via cell contact-dependent mechanisms. Notably, L. amazonensis amastigote infection failed to activate DCs, and this lack of DC activation could be partially reversed by the addition of preactivated NK (ANK) cells but not resting NK cells. Moreover, the adoptive transfer of ANK cells into L. amazonensis-infected mice markedly increased DC and T-cell activation and reduced tissue parasite loads at 1 and 3 weeks postinfection. These results suggest differential roles of DC-NK cell cross talk at different stages of Leishmania infection and provide new insight into the interplay of components of the innate immune system during parasitic infection.