Transcriptional response of macrophages to combined stimulation of NOD-like and Toll-like receptors (report 2)
AbstractIntroduction. Combinations of NOD-like and Toll-like receptor agonists are potent activators of macrophages. However, there is lack of detailed characteristics of transcriptional alterations occurring in macrophages stimulated by these agonists combinations.
Aim – to reveal and compare groups of genes characterized by increased and reduced expression upon combined stimulation of human macrophages with NOD1 and TLR4 agonists in vitro.
Material and methods. Macrophages generated from healthy donor monocytes were stimulated with NOD1 and TLR4 agonists separately or simultaneously during 1 or 4 hours. Transcriptomes were analysed using high-throughput RNA sequencing (RNA-seq) and bioinformatics.
Results. In macrophages stimulated with NOD1 + TLR4 agonist combination, we identified two groups of genes (> 500 genes each) characterized by either augmented or repressed mRNA expression. The inducible group was strongly enriched with genes encoding key inflammatory mediators, except for typical markers of M1 activation. The repressible group was enriched with genes coding for cell cycle regulators. Using bioinformatics approaches, we identified potential mechanisms that may underlie transcriptional reprogramming of macrophages in these activation conditions.
Conclusions. Combination of NOD1 and TLR4 agonists induces transcriptional reprogramming of macrophages compatible with innate type of activation.
Keywords:macrophages; transcriptome; NOD1; TLR4; muramyl peptides; lipopolysaccharide; RNA sequencing
For citation: Masyutina A.M., Pashenkov M.V. Transcriptional response of macrophages to combined stimulation of NOD-like and Toll-like receptors (report 2). Immunologiya. 2023; 44 (5): 534–44. DOI: https://doi.org/10.33029/1816-2134-2023-44-5-534-544 (in Russian)
Funding. The work was supported by the Russian Science Foundation grant No. 21-15-00211.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. Conducting experiments and analysing results – Masyutina A.M.; designing experiments, analysing results and writing the article – Pashenkov M.V.
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