Characterizing the Roles of ERK and NFkB in Macrophage Priming

Jazz Elaiza Q. Nario, Annalise Bond, Dr. Meghan Morrissey

As a key component of our immune system, macrophages monitor our tissues searching for harmful agents, such as cancer cells and pathogens. Upon detection of these subversive bodies, the macrophage engulfs the target cell in a process known as phagocytosis. Macrophage-mediated phagocytosis has been extensively studied, specifically antibody dependent cellular phagocytosis (ADCP) due to its significance to the pathophysiology of several life-threatening diseases. Emerging research has suggested that macrophages can hold a “memory” of previous stimuli, which is used to change their response with subsequent target encounters. This memory has not been studied in the context of ADCP. To address this gap, my mentor, Annalise Bond, has shown that macrophages can be primed or conditioned to have an enhanced response with subsequent targets during ADCP. However, the mechanisms of priming have yet to be characterized, specifically the roles of transcription factors ERK and NFkB. Using confocal microscopy, I will quantify phagocytic events from bead-eating assays performed with ERK and NFkB inhibitors at various timepoints after priming. If ERK and/or NFkB are involved in priming, their inhibition will result in a decrease of macrophage activity in primed macrophages when compared to primed macrophages in which ERK and NFkB are not inhibited. The results from the study will deepen our understanding of what affects macrophage appetite, suggesting new ways to better harness macrophages to robustly attack and eliminate cancer cells, as well contribute to the growing body of literature around innate immune memory.