Effect of bacteriophage-derived double stranded rna on rat peritoneal macrophages and microglia in normoxia and hypoxia

Abstract

The involvement of tissue-resident macrophages (TRMs) in health and diseases makes them unique therapeutic targets. TRMs are activated through their surface pattern recognition receptors, such as Toll-like receptors (TLRs) that are essential sensors of danger signals. Here, we determine the activation status of rat peritoneal macrophages (PMs) and microglia (MG) cells under normal and hypoxic conditions and investigate the effect of TLR3 agonist bacteriophage-derived dsRNA (Larifan) on the metabolic profile of TRMs in vitro. We implemented the phenotypic markers CD14 and CD206, arginine metabolism, phagocytic activity and reactive oxygen species generation as metabolic characteristics to evaluate TRMs activation. We showed that normoxic TRMs from different tissue niches responded to Larifan exposure in different ways. PM exhibited signs towards M1 polarisation. In contrast, the MG activation pattern could be considered as neither pro-inflammatory nor anti-inflammatory. We also showed that TRMs, regardless of the tissue niche, responded to hypoxia with a phenotypic shift towards an anti-inflammatory (M2) state. Larifan could attenuate hypoxia-induced TRMs metabolic programming. However, hypoxic conditions could negatively affect the interaction of TRMs with danger signals.