Paschalis Sideras, Georgios Divolis, Evgenia Synolaki and colleagues recently published a study in Frontiers in Immunology

Influenza is a common respiratory viral infection that may cause morbidity and mortality, especially among the elderly. In their study, Divolis et al. investigated the protective role of Activin-A, a member of the Transforming Growth Factor β superfamily, during Influenza infection. The authors showed that Activin-A produced by and acting on neutrophils dampened their activation towards Neutrophil Extracellular Trap (NET) release, leading to reduced lung tissue damage caused during Influenza infection, as monitored histologically and functionally. Moreover, transcriptome analysis of neutrophils deficient in Activin-A production revealed alterations consistent with a predisposition for NET release.  Collectively, these findings unveil a novel aspect of Activin-A as a feedback moderator of neutrophil-mediated and NETosis-driven collateral lung tissue damage with important therapeutic implications.

Exacerbated Neutrophil Extracellular Trap (NET) release by neutrophils in the lung tissue of animals with Activin-A deficient neutrophils (S100a8-Cre/Inhbafl/fl) versus control animals, following Influenza A Virus (IAV) infection. Images depict immunoreactivity of histone H3 or citrunilated-H3 (green) in lung sections, 15 days post-IAV infection. Arrowheads indicate clusters of NETotic cells. DAPI (blue) was used for nuclear staining.

Pubmed

Neutrophil-derived Activin-A moderates their pro-NETotic activity and attenuates collateral tissue damage caused by Influenza A virus infection
Divolis G, Synolaki E, Doulou A, Gavriil A, Giannouli CC, Apostolidou A, Foster ML, Matzuk MM, Skendros P, Galani IE, Sideras P. Front Immunol. 2024 Feb 26;15:1302489. doi: 10.3389/fimmu.2024.1302489. eCollection 2024. PMID: 38476229