C5aR2 Regulates STING-Mediated Interferon Beta Production in Human Macrophages
Citation:
Wright O, Harris A, Nguyen V.D, Zhou Y, Durand M, Jayyaratnam A, Gormley D, O� Neill L.A.J, Triantafilou K, Nichols E.M, Booty L.M, C5aR2 Regulates STING-Mediated Interferon Beta Production in Human Macrophages, Cells, 12, 23, 2023Download Item:
Abstract:
The complement system mediates diverse regulatory immunological functions. C5aR2, an enigmatic receptor for anaphylatoxin C5a, has been shown to modulate PRR-dependent pro-inflammatory cytokine secretion in human macrophages. However, the specific downstream targets and underlying molecular mechanisms are less clear. In this study, CRISPR-Cas9 was used to generate macrophage models lacking C5aR2, which were used to probe the role of C5aR2 in the context of PRR stimulation. cGAS and STING-induced IFN-β secretion was significantly increased in C5aR2 KO THP-1 cells and C5aR2-edited primary human monocyte-derived macrophages, and STING and IRF3 expression were increased, albeit not significantly, in C5aR2 KO cell lines implicating C5aR2 as a regulator of the IFN-β response to cGAS-STING pathway activation. Transcriptomic analysis by RNAseq revealed that nucleic acid sensing and antiviral signalling pathways were significantly up-regulated in C5aR2 KO THP-1 cells. Altogether, these data suggest a link between C5aR2 and nucleic acid sensing in human macrophages. With further characterisation, this relationship may yield therapeutic options in interferon-related pathologies.
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http://people.tcd.ie/laoneillDescription:
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Author: O'Neill, Luke
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Series/Report no:
Cells;12;
23;
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Full text availableKeywords:
complement, anaphylatoxin C5a, regulatory immunological functions, interferon beta, cGAS-STING, innate immune sensing, C5a, anaphylatoxin receptor, C5aR2, pattern recognition receptorDOI:
http://dx.doi.org/10.3390/cells12232707Metadata
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