Final Report Summary - STEPS (Signalling compartmentalization and vesicle Trafficking at the Phagocytic Synapses)
Macrophages are an heterogeneous population of immune cells playing several and diverse functions in homeostatic and immune responses. The broad spectrum of macrophage functions relies on both the heterogeneity and plasticity of these cells, which are highly specialized in sensing the microenvironment and modify their properties accordingly.
Macrophages have direct, crucial and complex roles in both infectious and inflammatory diseases but the cellular and molecular mechanisms responsible for tuning macrophage responses are still elusive, and this represents a major obstacle for the development of new treatments.
The aim of my ERC Advanced project, STePS, was to provide a deeper understanding of the molecular interactions leading to macrophage activation. In particular, we focused on the role of mitochondria in macrophage activation and functions.
Mitochondria are dynamic organelles controlling multiple cell functions, including signalling, metabolism, and cell death. In addition, these organelles are engaged in the regulation of inflammatory responses through mechanisms involving generation of reactive oxygen species (ROS), release of damage-associated molecular patterns (DAMPs), Ca2+ buffering, and production of metabolites.
STePS identified novel signalling pathways controlling macrophage activation and inflammation. Most of these pathways involve mitochondrial proteins with various roles in mitochondria biology (calcium buffering, shape control, metabolism).
These results may offer novel therapeutic targets and strategies to treat chronic inflammatory diseases.
Macrophages have direct, crucial and complex roles in both infectious and inflammatory diseases but the cellular and molecular mechanisms responsible for tuning macrophage responses are still elusive, and this represents a major obstacle for the development of new treatments.
The aim of my ERC Advanced project, STePS, was to provide a deeper understanding of the molecular interactions leading to macrophage activation. In particular, we focused on the role of mitochondria in macrophage activation and functions.
Mitochondria are dynamic organelles controlling multiple cell functions, including signalling, metabolism, and cell death. In addition, these organelles are engaged in the regulation of inflammatory responses through mechanisms involving generation of reactive oxygen species (ROS), release of damage-associated molecular patterns (DAMPs), Ca2+ buffering, and production of metabolites.
STePS identified novel signalling pathways controlling macrophage activation and inflammation. Most of these pathways involve mitochondrial proteins with various roles in mitochondria biology (calcium buffering, shape control, metabolism).
These results may offer novel therapeutic targets and strategies to treat chronic inflammatory diseases.