Resolvin D1 and D2 reduce SARS?CoV?2?induced inflammatory responses in cystic fibrosis macrophages

An excessive, non-resolving inflammatory response underlies severe COVID-19 that may have fatal outcomes. Therefore, the investigation of endogenous pathways leading to resolution inflammation is interest uncover strategies for mitigating in people with SARS-CoV-2 infection. This becomes particularly urgent individuals preexisting pathologies characterized by chronic respiratory and prone bacterial infection, such as cystic fibrosis (CF). Here, we analyzed immune responses virion spike 1 glycoprotein (S1) macrophages (M?) from volunteers without CF tested efficacy resolvins (Rv) D1 D2 regulating antimicrobial functions M? exposed S1. S1 significantly increased chemokine release, including interleukin (IL)-8, non-CF M?, while it enhanced IL-6 tumor necrosis factor (TNF)-? but not cells. also triggered biosynthesis RvD1 modulated microRNAs miR-16, miR-29a, miR-103, known control responses. RvD2 treatment abated S1-induced reducing release select chemokines cytokines IL-8 TNF-?. both restored expression miR-16 selectively increasing miR-223 miR-125a, which are involved NF-?B activation polarization. During Pseudomonas aeruginosa stimulated phagocytic activity was further RvD2. These results provide a map molecular key determinants COVID-19-related inflammation, unveiling some peculiarity cells CF. They demonstrate beneficial, regulatory actions on SARS-CoV-2-induced inflammation.