Update of cellular responses to the efferocytosis of necroptosis and pyroptosis

Chandra Agung Purnama, Anna Meiliana, Melisa Intan Barliana, Keri Lestari

Cell death is a basic physiological process that occurs in all living organisms. A few key players in these mechanisms, as well as various forms of cell death programming, have been identified. Apoptotic cell phagocytosis, also known as apoptotic cell clearance, is a well-established process regulated by a number of molecular components, including 'find-me', 'eat-me' and engulfment signals. Efferocytosis, or the rapid phagocytic clearance of cell death, is a critical mechanism for tissue homeostasis. Despite having similar mechanism to phagocytic clearance of infections, efferocytosis differs from phagocytosis in that it induces a tissue-healing response and is immunologically inert. However, as field of cell death has rapid expanded, much attention has recently been drawn to the efferocytosis of additional necrotic-like cell types, such as necroptosis and pyroptosis. Unlike apoptosis, this method of cell suicide allows the release of immunogenic cellular material and causes inflammation. Regardless of the cause of cell death, the clearance of dead cells is a necessary function to avoid uncontrolled synthesis of pro-inflammatory molecules and inflammatory disorder. We compare and contrast apoptosis, necroptosis and pyroptosis, as well as the various molecular mechanisms of efferocytosis in each type of cell death, and investigate how these may have functional effects on different intracellular organelles and signalling networks. Understanding how efferocytic cells react to necroptotic and pyroptotic cell uptake can help us understand how to modulate these cell death processes for therapeutic purposes.