P.373 Inflammatory control of stress response and vulnerability to depression

Abstract

The complement system contributes to host defense against various types of pathogens as part of the innate immune system and to the disposal of abnormal host cells. Its activation leads to elimination of the targeted elements via direct lysis or phagocytic capture as well as to local inflammation and is therefore tightly controlled by several specific checkpoints. Besides these well-recognized functions, recent studies have revealed a variety of additional roles. Among those, is an unanticipated connection between components of the complement system and macro-autophagy, the evolutionarily conserved intracellular pathway that directs cytosolic materials to endo-lysosomal compartments for degradation and recycling after encapsulating them into unique vesicles called autophagosomes. Factors of the complement system can efficiently initiate or modulate the autophagy process through ligand-receptor interactions taking place at the level of cell membranes but also intracellularly via direct interaction with core autophagy factors. The connection between the complement system and the autophagy machinery can mobilize the cell autonomous defense function of autophagy against intracellular microbes but can also be effective in supporting other functions such as metabolism regulation or tissue remodeling during development. This chapter focuses on our current knowledge of the mechanisms involved in the complement system-autophagy relationship, as well as on questions raised by the discovery of these mechanisms.