Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells

J Martinez, J Almendinger, A Oberst… - Proceedings of the …, 2011 - National Acad Sciences
J Martinez, J Almendinger, A Oberst, R Ness, CP Dillon, P Fitzgerald, MO Hengartner
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
The recognition and clearance of dead cells is a process that must occur efficiently to
prevent an autoimmune or inflammatory response. Recently, a process was identified
wherein the autophagy machinery is recruited to pathogen-containing phagosomes, termed
MAPLC3A (LC3)-associated phagocytosis (LAP), which results in optimal degradation of the
phagocytosed cargo. Here, we describe the engagement of LAP upon uptake of apoptotic,
necrotic, and RIPK3-dependent necrotic cells by macrophages. This process is dependent …
The recognition and clearance of dead cells is a process that must occur efficiently to prevent an autoimmune or inflammatory response. Recently, a process was identified wherein the autophagy machinery is recruited to pathogen-containing phagosomes, termed MAPLC3A (LC3)-associated phagocytosis (LAP), which results in optimal degradation of the phagocytosed cargo. Here, we describe the engagement of LAP upon uptake of apoptotic, necrotic, and RIPK3-dependent necrotic cells by macrophages. This process is dependent on some members of the classical autophagy pathway, including Beclin1, ATG5, and ATG7. In contrast, ULK1, despite being required for autophagy, is dispensable for LAP induced by uptake of microbes or dead cells. LAP is required for efficient degradation of the engulfed corpse, and in the absence of LAP, engulfment of dead cells results in increased production of proinflammatory cytokines and decreased production of anti-inflammatory cytokines. LAP is triggered by engagement of the TIM4 receptor by either phosphatidylserine (PtdSer)-displaying dead cells or PtdSer-containing liposomes. Therefore, the consequence of phagocytosis of dead cells is strongly affected by those components of the autophagy pathway involved in LAP.
National Acad Sciences