Neutrophil-derived Activin-A moderates their pro-NETotic activity and attenuates collateral tissue damage caused by Influenza A virus infection.

Background

Pre-neutrophils, while developing in the bone marrow, transcribe the

Methods

To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model (

Results

We found that neutrophil-specific Activin-A deficiency led to exacerbated pulmonary inflammation and widespread hemorrhagic histopathology in the lungs of IAV-infected animals that was associated with an exuberant production of neutrophil extracellular traps (NETs). Moreover, deletion of the Activin-A receptor ALK4/ACVR1B in neutrophils exacerbated IAV-induced pathology as well, suggesting that neutrophils themselves are potential targets of Activin-A-mediated signaling. The pro-NETotic tendency of Activin-A-deficient neutrophils was further verified in the context of thioglycollate-induced peritonitis, a model characterized by robust peritoneal neutrophilia. Of importance, transcriptome analysis of Activin-A-deficient neutrophils revealed alterations consistent with a predisposition for NET release.

Conclusion

Collectively, our data demonstrate that Activin-A, secreted by neutrophils upon their activation in the periphery, acts as a feedback mechanism to moderate their pro-NETotic tendency and limit the collateral tissue damage caused by neutrophil excess activation during the inflammatory response.

Informations de copyright

Copyright © 2024 Divolis, Synolaki, Doulou, Gavriil, Giannouli, Apostolidou, Foster, Matzuk, Skendros, Galani and Sideras.

Déclaration de conflit d'intérêts

All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.