Research Projects

Apoptotic death in the human body clears about 300 billion cells daily, which amounts to about 4 million cells per second!1 These apoptotic cells display phosphatidyl serine (PS) on their surface, and are thus recognised by neighbouring phagocytes by means of PS receptors leading to their engulfment and clearance - a phenomenon called efferocytosis2. Efferocytosis is a ubiquitous process and engulfment of apoptotic cells induces rapid changes in the gene expression program in the engulfing phagocyte causing it to adopt an anti-inflammatory and pro-wound healing phenotype. This process is driven by metabolites that are derived by the digestion of the engulfed cargo3. Hence apoptosis is not merely the death of a cell and apoptotic bodies bear the signature of the dying cell and are capable of transmitting the “information” to the neighbourhood. It is a well understood fact that not all cells in the body are metabolically similar and chronic inflammation associated pathologies like atherosclerosis and diabetes etc. fundamentally modify the metabolic behaviour of immune cells like macrophages4, while also triggering their cell death. We hypothesize that the metabolically modified apoptotic cargo generated during the course of inflammatory pathologies is grossly distinct from homeostatic apoptosis. This culminates into an “altered messaging” being sent out to bystander phagocytic cells in their vicinity, thus altering their efferocytic behaviour. Further, we hypothesize that the engulfment and subsequent digestion of this metabolically altered cargo rewires the immunometabolic landscape of the phagocytic cells in a manner distinct from that observed under homeostatic efferocytosis and these changes have significant bearing on inflammation resolution.