Innate Apoptotic Immunity: Characterization of Macrophage Responses

About 10^11 cells die daily by apoptosis (programmed physiological cell death) in the human body. Cells dying by apoptosis are rapidly engulfed and digested by their neighbors or by professional phagocytes in a process of phagocytosis, such that we are barely able to detect apoptotic cells in vivo normally. During the process of apoptosis, cells acquire a distinct “gain-of-function” trait which triggers a milieu of signaling events in the neighboring interacting cells, leading to an immunosuppressive (especially anti-inflammatory) state. While the mechanisms of apoptosis and those of clearance of effete cells have been studied extensively, those related to this gain-of-function accompanying apoptosis are much less understood. Perhaps the ultimate objective of the apoptotic process, along with the efficient elimination of inappropriate and non-functional cells, is to restore a physiological (non-inflammatory, “calm”) setting. Understanding this immunosuppressive activity of apoptotic cells, which we have termed “Innate Apoptotic Immunity (IAI), is the focus of this thesis.