Memory-like NK cells protective roles or lack thereof in uncomplicated and severe malaria 2107

Abstract Description We need to better understand the immune response to the erythrocytic stage of malaria. We found that natural killer cells could inhibit the growth of Plasmodium infected RBCs via antibody dependent cellular cytotoxicity (ADCC). We therefore assessed ADCC in a large malaria cohort and found memory-like NK cells lacking Fc γ chain correlated with clinical immunity and reduced parasitemia. This memory-like NK cell subset had increased ADCC and IFNγ production. However, after CRISPR ablating the Fc γ chain gene, there was no effect on ADCC function. Thankfully, we found an alternative molecule, Siglec 7, that was also down regulated and when ablated did increase ADCC and IFNγ production. We hypothesize these Siglec 7 neg memory-like NK cells are protective because they are better at killing infected RBCs via ADCC. This was bolstered by our recent finding that NK cells from severe malaria subjects had reduced killing function. However, we still didn’t have a clear explanation for why more IFNγ would correlate with reduced clinical immunity in uncomplicated malaria. Recently, we found NK cells make more IL-10 in malaria exposed people. We therefore hypothesize memory-like NK cells are protective because they can both decrease parasitemia through ADCC and produce IL-10 to limit pathological inflammation over time. The important theme of this research is that increased or decreased NK cell function correlates with either protection or susceptibility respectively to malaria symptoms. Funding Sources NIH R01AI146031 NIH R01AI143828 NIH R21AI149659 University of Minnesota - Medical School University of Minnesota - Department of Medicine University of Minnesota - Division of Infectious Disease and International Medicine Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)