Role of Natural Killer and Dendritic Cell in Immunomodulation

Early stages of infections are associated with local recruitment and activation of dendritic cells (DC) and NK cells. Although activated DC and NK cells are known to support each other's functions, both in the periphery and in the secondary lymphoid organs. Thus, NK cells’ activation by dendritic cells allows the killing of transformed or infected cells in the periphery but may also be important for the generation of adaptive immunity. This regulatory role of DC/NK cross-talk is of particular importance at mucosal surfaces such as the intestine, where the immune system exists in intimate association with commensal bacteria such as lactic acid bacteria (LAB). NK cells are capable of inducing stable type 1-polarized “effector/memory” DC (DC1) that act as carriers of NK cell-derived helper signals for the development of type 1 immune responses. NK induced DC1 prime naive CD4⁺ Th cells for high levels of IFN-γ, but low IL-4 production, and demonstrate a strongly enhanced ability to induce Ag-specific CD8⁺ T cell responses. Resting NK cells display stringent activation requirements to perform this novel, DC-mediated, “helper” function. Helper activity of NK cells may support the development of Th1- and CTL-dominated type 1 immunity against intracellular pathogens. NK/DC interactions in the presence of gut-derived commensal bacteria and their role in bacterial straindependent immunomodulatory effects. This highlight the ability of distinct species of commensal bacterial probiotics to differently affect the outcome of DC/NK cross-talk and consequently to differently influence the polarization of the adaptive immune response.