AbstractInnate lymphoid cells, including natural killer cells contribute significantly to the immune response to viral and parasitic infections. Substantial geographical differences are observed in the differentiation phenotype of these cells are observed comparing high and low/middle income settings with potentially significant impact on their functional capacity. We observe rapid differentiation of the NK cell compartment with the emergence of high frequency, adaptive human cytomegalovirus associated expansions (FcR1-PLZF-CD57+NKG2C+) occurring in early life in Gambians. These changes are associated with adaptation of the NK cell compartment away from dependence on cytokine-mediated signals and towards immunoglobulin Fc Receptor-mediated activation. We demonstrate the impact of this adaptation on responses to Plasmodium falciparum infected erythrocytes. Evidence will also be presented on how vaccines promote NK cell effector responses according to their functional differentiation in European and African settings. The detection and differentiation potential of other blood innate lymphoid cell subsets will also be discussed.