Influence of IL-10 on Mitochondrial Function of Dendritic Cells After Efferocytosis of Infected Cells

• Grant number: 24/04671-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2024
• Effective date (End): May 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Fernanda Ragonese
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

During cutaneous infection by methicillin-resistant Staphylococcus aureus (MRSA), neutrophils are recruited and phagocytose the bacteria for digestion, subsequently undergoing cell death. Infected apoptotic neutrophils in the skin can be phagocytosed by dendritic cells, Langerhans cells, and macrophages. Phagocytosis of apoptotic cells, termed efferocytosis, demands energy for cytoskeletal rearrangement and digestion of the apoptotic body. It is known that this energy source primarily originates from the glycolytic pathway, due to its rapid conversion of pyruvate to lactate, releasing energy in the form of ATP (adenosine triphosphate). Recent data obtained by our research group demonstrate that phagocytosis of apoptotic cells infected with MRSA (MRSA-iAC) results in reduced mitochondrial respiration, increased production of mitochondrial reactive oxygen species (ROS), and a percentage of dysfunctional mitochondria in dendritic cells (DCs) after 6 hours of efferocytosis. However, after 18 hours, restoration of mitochondrial function and decreased glycolytic pathway were observed. Restoration of mitochondrial function was accompanied by increased secretion of IL-10 by DCs, after 18 hours of MRSA-iAC efferocytosis. Based on previous literature demonstrating that the cytokine IL-10 is a potent inducer of mitophagy in LPS-activated macrophages and capable of reducing mitoROS production, the hypothesis of this study is that IL-10 assists in restoring mitochondrial function and negatively regulating glycolysis in BMDCs after efferocytosis of MRSA-iAC at later time points. Thus, the aim of this study is to evaluate the role of IL-10 in restoring mitochondrial functions, including mitochondrial membrane potential, and reducing ROS production during efferocytosis of MRSA-iAC.