Treatment with lipoxin A4 improves Influenza A infection outcome through macrophage reprogramming, anti-inflammatory and pro-resolutive response 3814

Abstract Description Influenza A is responsible for high numbers of mortality and morbidity. Nowadays, the most efficient intervention is vaccination and some ant- inflammatory therapies, therefore it is important to study new molecules as potential candidates to treat that infection. Lipoxin A4 is a pro-resolving mediator known not only for decreasing cell recruitment and pro-inflammatory cytokines but also for inducing activation of apoptosis and macrophage reprogramming. Here, we studied the use of lipoxin A4 as a therapeutic strategy to treat Influenza A infection. Mice were infected with Influenza A/H1N1 and treated with lipoxin A4 via intraperitoneal, starting on day 3 post infection up to the day of euthanasia. Treated mice presented increased survival with decreased cell recruitment and lung damage. The treatment was able to modulate macrophage reprogramming decreasing classically activated macrophages (M1) marker iNOS,and increasing alternatively activated macrophages (M2) marker arginase 1, in the lungs. Furthermore, the number of apoptotic cells and cells under efferocytosis was increased in the BALF of the treated mice. Lipoxin A4 modulated the adaptive immune response increasing the number of Th2 and regulatory T cells in the lungs of the treated mice. In addition, we showed that lipoxin A4 protection was FPR2-dependent. These results show a promising therapeutic effect of lipoxin A4 in a model of Influenza A infection, contributing to ananti-inflammatory and pro-resolving scenario. Funding Sources NIH HL10738; 476071/2011-9 CNPq; 309810/2017-5 FAPEMIG Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)