Bacteriophage derived dsRNA induces polarized activation of alveolar macrophages from Balb/c and C57Bl/6 mice in vitro in sex- and age-dependent manner

Bacteriophage-derived dsRNA (bp-dsRNA), also known as Larifan, is a poly-functional and wide-spectrum antiviral medication with potent interferonogenic activity. In the lungs of golden Syrian hamsters infected with SARS-CoV-2, Larifan substantially reduces viral load and decreases infection-induced pathological lesion severity. Alveolar macrophages (AM) are key sentinel cells in the lung, which play an important role in antiviral innate immune responses and, at the same time, can trigger infection-associated hyper-inflammatory response. This study revealed that treatment with bp-dsRNA (Larifan) in vitro modulates the functional profile of AM from intact Balb/c and C57Bl/6 mice. The pattern of the drug response depends on the animal strain, age and sex. AM from Balb/c mice generated a weaker response to the preparation as compared to cells from C57Bl/6 mice. Most emphatic responses to the treatment with bf-dsRNA (Larifan) were registered in AM from old males of both BALB/c and C57BL/6 strains with the strongest in the latter. AM from old C57BL/6 females were less likely to be influenced by the preparation. In most cases, exposure to bf-dsRNA (Larifan) increased AM phagocytic activity and was more often accompanied by the stimulation of intracellular reactive oxygen species generation, than by its decrease. In most animal groups, treatment with bf-dsRNA (Larifan) did not affect significantly CD206 expression and down-regulated CD80 expression in AM. Taken together, our findings suggest that bf-dsRNA (Larifan) not so much stimulates the bivalent phenotype of AM, as restrains their hyper-inflammatory responses through the control of antigen-presentation while preserving functional signatures typical of patrolling tissue-resident macrophages.