Ben Zandstra

Malaria, a parasitic disease caused by plasmodium, is transmitted by female Anopheles mosquitoes developing in infected liver cells which then go on to infect red blood cells. Among infected individuals, sterile immunity is almost never achieved, which involves the prevention of the malaria parasite from infecting liver cells and progressing to the blood stage. Clinical immunity, which is achieved from constant exposure, describes reduced inflammation and parasitic load from the blood stage parasite. Much of the immune response, which provides infected individuals with clinical immunity, relies on the production of antibodies to prevent parasitic replication in the blood stage. One mechanism by which antibodies help clear infection is through antibody Fc receptor mediated lysis from natural killer (NK) cells, also known as antibody dependent cellular cytotoxicity (ADCC). The phenotype of NK cells that reduce malaria parasite load via ADCC is unclear. A Subset of NK cells, described as adaptive NK cells, have enhanced ADCC function. These adaptive NK cells have faster response to infection and have increased ADCC functionality from antibody Fc receptor activation. Preliminary data from our lab shows that NK cells from patients with a history of malaria infection are largely Siglec-7 negative. To further examine the role of the Siglec-7 receptor in ADCC, Siglec-7 was knocked out via CRISPR-Cas-9 and accessed using three in vitro killing assays. Siglec-7 knockout cells showed increased degranulation, and target cell lysis compared to controls. This suggests that Siglec-7 negative NK cells may be an important immunological marker for adaptive NK cells in malaria.