The interplay between apoptotic cells and macrophages: impact on the phenotype and function of macrophages

Abstract

Macrophages are a heterogeneous population of innate myeloid cells which appear in every tissue. Depending on their environment, they exert numerous tissue-associated functions as reflected by their transcriptional heterogeneity. The capacity to phagocytose foreign or damaged cells is a common function of macrophages across all tissues and is performed during their whole life span. The constant clearance of apoptotic cells by macrophages is essential for the functionality of the immune system. In particular, phagocytosis of apoptotic cells in the presence of IL-4 and IL-13 drives macrophages towards an anti-inflammatory/tissue remodelling phenotype. Although apoptotic corpses might originate from different cells, up to now they have been defined only by typical morphological changes such as the exposure of phosphatidylserine, membrane blebbing and DNA fragmentation. The data presented in this thesis demonstrate that apoptotic cells are, in fact, a heterogeneous population of cells, which differentially imprint the transcriptome and function of macrophages in dependency of their original identity.