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Loss of Siglec-7 drives enhanced NK cell function and correlates with protection from malaria symptoms
Presentation Time: 10:00 AM - 10:15 AM
Abstract ID: 4180 - B
Presenting Author: Jenna K Dick Abstract:
Plasmodium falciparum (P.f) infection is major cause of morbidity and mortality world-wide and deaths occur because of the blood stage of the P.f. life cycle. To date, there is no effective blood stage malaria vaccine. Natural killer (NK) cells inhibit the growth of Pf. in the bloodthrough antibody dependent cellular cytotoxicity (ADCC). A subset of NK cells in malaria lack the Fc receptor gamma chain and have enhanced ADCC. However, it is unclear if the lack of FcR gamma chain is the reason for increased functionality or if it only serves as a marker. Using CRIPSR/Cas9, we found that ablating the FcR gamma chain did not enhance ADCC. We then searched for other alterations in malaria NK cells that could explain the enhanced functionality. Using cohort of subjects from a malaria clinical study in Mali, Africa, we found that the expression of Sigelc-7, an inhibitory receptor, correlates with FcR gamma chainexpression and that decreased expression of Siglec-7 correlates with increased ADCC function. Using CRISPR/Cas9, we then ablated Siglec-7 and show enhanced ADCC and killing of P.f-infected red blood cells in NK cells that lacked Siglec-7. Furthermore, Siglec-7 negative NK cells correlate with lower parasitemia and protection from malaria. These data provide evidence that the host may increase the number of Siglec-7 negative NK cells to aide in the clearance of infected RBCs through ADCC. These results can be leveraged in developing effective blood stage vaccines.
Loss of Siglec-7 drives enhanced NK cell function and correlates with protection from malaria symptoms
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 10:00 AM to 10:15 AM Room: Room W176