Phagocyte responses during apoptotic cell clearance in the resolution of inflammation

Principal investigator: Noelia Alonso Gonzalez
Project number: CRC 1450 C02
Project term: 01/2021–12/2028

Receptor engagement during organ-specific efferocytosis. Efferocytosis is performed upon recognition of “eat-me” signals present in the outer membrane of apoptotic cells. Tissue-resident macrophages posses a wide variety of phagocytic receptors that vary across tissue, and that engage in the recognition and following phagocytosis of the apoptotic cargo (A). We aim to elucidate the specific role of MARCO in the regulation of other phagocytic receptors, and how this influences efferocytosis and the resolution of inflammation in an organ-specific manner (B).
© CRC inSight C02

The aim of this project is to design apoptotic cell clearance based approaches to improve the resolution of inflammation. We have identified several mechanisms that confer peritoneal macrophages with an extraordinary efficiency clearing dead cells through phagocytosis. The use of MARCO-deficient mice revealed a tissue-specific regulation of efferocytosis in peritoneal macrophages. Based on those results, we have genetically engineered ER-HoxB8 cell lines overexpressing MARCO, which show a higher potential of phagocytosis. Moreover, comparative analysis of tissue-resident macrophages revealed diverse regulatory patterns of other phagocytic receptors in response to bacterial triggers. Therefore, our current focus is to study receptor engagement in tissue-resident macrophages during acute inflammation, analysing its role in efferocytosis and tissue repair. Combined with a multiscale imaging approach in mouse models of acute inflammation, we will elucidate the mechanisms of efferocytosis-mediated inflammatory resolution in an organ-specific manner.

Team

Principal investigator

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Publications

The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.