Relevance of Angiotensin-(1-7) and its receptor Mas in pneumonia caused by Influenza virus and post-influenza pneumococcal infection

Item Type:	Article
Title:	Relevance of Angiotensin-(1-7) and its receptor Mas in pneumonia caused by Influenza virus and post-influenza pneumococcal infection
Creators Name:	Melo, E.M. and Del Sarto, J. and Vago, J.P. and Tavares, L.P. and Rago, F. and Gonçalves, A.P.F. and Machado, M.G. and Aranda-Pardos, I. and Valiate, B.V.S. and Cassali, G.D. and Pinho, V. and Sousa, L.P. and A-Gonzalez, N. and Campagnole-Santos, M.J. and Bader, M. and Santos, R.A.S. and Machado, A.V. and Ludwig, S. and Teixeira, M.M.
Abstract:	Resolution failure of exacerbated inflammation triggered by Influenza A virus (IAV) prevents return of pulmonary homeostasis and survival, especially when associated with secondary pneumococcal infection. Therapeutic strategies based on pro-resolving molecules have great potential against acute inflammatory diseases. Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator that acts on its Mas receptor (MasR) to promote resolution of inflammation. We investigated the effects of Ang-(1-7) and the role of MasR in the context of primary IAV infection and secondary pneumococcal infection and evaluated pulmonary inflammation, virus titers and bacteria counts, and pulmonary damage. Therapeutic treatment with Ang-(1-7) decreased neutrophil recruitment, lung injury, viral load and morbidity after a primary IAV infection. Ang-(1-7) induced apoptosis of neutrophils and efferocytosis of these cells by alveolar macrophages, but had no direct effect on IAV replication in vitro. MasR-deficient (MasR(-/-)) mice were highly susceptible to IAV infection, displaying uncontrolled inflammation, increased viral load and greater lethality rate, as compared to WT animals. Ang-(1-7) was not protective in MasR(-/-) mice. Interestingly, Ang-(1-7) given during a sublethal dose of IAV infection greatly reduced morbidity associated with a subsequent S. pneumoniae infection, as seen by decrease in the magnitude of neutrophil influx, number of bacteria in the blood leading to a lower lethality. Altogether, these results show that Ang-(1-7) is highly protective against severe primary IAV infection and protects against secondary bacterial infection of the lung. These effects are MasR-dependent. Mediators of resolution of inflammation, such as Ang-(1-7), should be considered for the treatment of pulmonary viral infections.
Keywords:	Influenza Virus, Streptococcus Pneumoniae, Angiotensin-(1-7), Inflammation, Resolution, Infection, Animals, Dogs, Mice
Source:	Pharmacological Research
ISSN:	1043-6618
Publisher:	Elsevier
Volume:	163
Page Range:	105292
Date:	January 2021
Official Publication:	https://doi.org/10.1016/j.phrs.2020.105292
PubMed:	View item in PubMed

Repository Staff Only: item control page