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C5aR2 regulates STING-mediated interferon beta production in human macrophages

ABSTRACT: The complement system mediates diverse regulatory effects across the immune system. 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 defined. 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 expression of STING and IRF3 was increased 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 cell lines. These results suggest that C5aR2 is a negative regulator of nucleic acid sensing in macrophages, with potential relevance for viral infection and anti-tumour immunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245973 | GEO | 2023/10/22

REPOSITORIES: GEO

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