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Complement C5a Receptor Signaling in Macrophages Enhances Trained Immunity Through mTOR Pathway Activation

  • Eun-Hyeon Shim (Innovative Research and Education Center for Integrated Bioactive Materials and the Department of Bioactive Material Sciences, Jeonbuk National University) ;
  • Sae-Hae Kim (Department of Molecular Biology and The Institute for Molecular Biology and Genetics, Jeonbuk National University) ;
  • Doo-Jin Kim (Department of Medicine, College of Medicine and Medical Research Institute, Chungbuk National University) ;
  • Yong-Suk Jang (Innovative Research and Education Center for Integrated Bioactive Materials and the Department of Bioactive Material Sciences, Jeonbuk National University)
  • Received : 2024.01.09
  • Accepted : 2024.05.31
  • Published : 2024.08.31
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Abstract

Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program (2019R1A2C2004711 to Yong-Suk Jang and 2021R1I1A1A01059681 to Sae-Hae Kim) and (2017R1A6A1A03015876 to Yong-Suk Jang) of the National Research Foundation (NRF), funded by the Korean Ministry of Science and ICT and the Korean Ministry of Education, respectively. Dr. Yong-Suk Jang was supported by the "Research Base Construction Fund Support Program" funded by Jeonbuk National University in 2024. Eun-Hyeon Shim was supported by the BK21 FOUR program in the Department of Bioactive Material Sciences. Cytological studies were performed using the instruments installed in the Center for University-Wide Research Facilities (CURF) at Jeonbuk National University.

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