Lysis of RBCs by NK cells in the presence of Abs bound to the RBCs was measured by several independent assays. There was no difference in hemoglobin release between RBCs and infected RBCs after incubation with primary human NK cells in the presence of a rabbit polyclonal anti-RBC rabbit serum. Therefore, P.f.-infected RBCs are not inherently resistant to NK-mediated ADCC. Efficient granzyme B delivery into infected RBCs was detected using reporter probes that fluoresce after granzyme B-mediated proteolytic cleavage. The results confirmed those of hemolysis assays. Lysis of infected RBCs was also detected in the presence of human sera from adults living in a malaria endemic region in Mali, but not from US adults. Finally, preliminary parasite growth inhibition assays indicated that ADCC by NK cells reduced the infection of freshly added RBCs. NK cell phenotype and function was examined in individuals chronically exposed to malaria. NK cells in blood samples of 216 individuals living in Kalifabougou, Mali were examined by multi-parameter flow cytometry. The cohort included individuals from 2 to 20-years of age. Blood samples were collected before, during, and after malaria transmission season. The data collection has been completed. We are using generalized linear models (GLM) to determine which NK phenotypic and functional parameters predict clinical immunity, taking into account factors such as parasitemia, age, and seasonal changes in the Malian cohort. Multivariate analysis by Barnes-Hut t-distributed stochastic neighbor embedding (t-SNE) is underway.
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