In:
Open Biology, The Royal Society, Vol. 11, No. 3 ( 2021-03)
Abstract:
Nucleic acid sensing through pattern recognition receptors is critical for immune
recognition of microbial infections. Microbial DNA is frequently methylated at the N 6 position of adenines (m6A), a modification that is rare in
mammalian host DNA. We show here how that m6A methylation of 5′-GATC-3′ motifs augments the immunogenicity of synthetic
double-stranded (ds)DNA in murine macrophages and dendritic cells. Transfection with m6A-methylated DNA increased the expression of the activation markers CD69
and CD86, and of Ifnβ , iNos and Cxcl10 mRNA. Similar to unmethylated cytosolic dsDNA,
recognition of m6A DNA occurs independently of TLR and RIG-I signalling, but requires the two key mediators of cytosolic DNA sensing, STING and cGAS.
Intriguingly, the response to m6A DNA is sequence-specific. m6A is immunostimulatory in some motifs, but immunosuppressive in others, a feature
that is conserved between mouse and human macrophages. In conclusion, epigenetic alterations of DNA depend on the context of the sequence and are differentially
perceived by innate cells, a feature that could potentially be used for the design of immune-modulating therapeutics.
Type of Medium:
Online Resource
ISSN:
2046-2441
Language:
English
Publisher:
The Royal Society
Publication Date:
2021
detail.hit.zdb_id:
2630944-0