Complement C5a Receptor Signaling in Macrophages Enhances Trained Immunity Through mTOR Pathway Activation
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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.
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.
참고문헌 (22)
- Walport MJ, "Complement. First of two parts", N Engl J Med, 344, pp.1058~1066 (2001)
- Pandey S, "Emerging insights into the structure and function of complement C5a receptors", Trends Biochem Sci, 45, pp.693~705 (2020)
- Mastellos DC, "A guide to complement biology, pathology and therapeutic opportunity", Nat Rev Immunol, 24, pp.118~141 (2024)
- Seow V, "Inflammatory responses induced by lipopolysaccharide are amplified in primary human monocytes but suppressed in macrophages by complement protein C5a", J Immunol, 191, pp.4308~4316 (2013)
- Yuk JM, "TNF in human tuberculosis : a double-edged sword", Immune Netw, 24, pp.e4~ (2024)
- Desai JV, "C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection", Cell, 186, pp.2802~2822 (2023)
- Sun L, "Attenuation of IgG immune complex-induced acute lung injury by silencing C5aR in lung epithelial cells", FASEB J, 23, pp.3808~3818 (2009)
- Horng T, "mTOR trains heightened macrophage responses", Trends Immunol, 36, pp.1~2 (2015)
- Cheng SC, "mTOR-and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity", Science, 345, pp.1250684~ (2014)
- Cirovic B, "BCG vaccination in humans elicits trained immunity via the hematopoietic progenitor compartment", Cell Host Microbe, 28, pp.322~334 (2020)
- Jeyanathan M, "Parenteral BCG vaccine induces lung-resident memory macrophages and trained immunity via the gut-lung axis", Nat Immunol, 23, pp.1687~1702 (2022)
- Pulendran B, "Emerging concepts in the science of vaccine adjuvants", Nat Rev Drug Discov, 20, pp.454~475 (2021)
- Kim SH, "C5aR+ dendritic cells fine-tune the Peyer’s patch microenvironment to induce antigen-specific CD8+ T cells", NPJ Vaccines, 8, pp.120~ (2023)
- Kim SH, "The M cell-targeting ligand promotes antigen delivery and induces antigen-specific immune responses in mucosal vaccination", J Immunol, 185, pp.5787~5795 (2010)
- Kim SH, "Complement C5a promotes antigen cross-presentation by Peyer’s patch monocyte-derived dendritic cells and drives a protective CD8+ T cell response", Cell Reports, 35, pp.108995~ (2021)
- Saz-Leal P, "Targeting SHIP-1 in myeloid cells enhances trained immunity and boosts response to infection", Cell Reports, 25, pp.1118~1126 (2018)
- Ochando J, "Trained immunity-basic concepts and contributions to immunopathology", Nat Rev Nephrol, 19, pp.23~37 (2023)
- de Haas CJ, "Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent", J Exp Med, 199, pp.687~695 (2004)
- Sánchez-Ramón S, "Trained immunity-based vaccines : a new paradigm for the development of broad-spectrum anti-infectious formulations", Front Immunol, 9, pp.2936~ (2018)
- aYan J, "A protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens", Sci Transl Med, 15, pp.eadf9556~ (2023)
- Lee A, "BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance", Nat Immunol, 25, pp.41~53 (2024)
- Scheid A, "Adjuvant effect of Bacille Calmette-Guerin on hepatitis B vaccine immunogenicity in the preterm and term newborn", Front Immunol, 9, pp.29~ (2018)
