PT  - JOURNAL ARTICLE
AU  - Melanie Brügger
AU  - Thomas Démoulins
AU  - G. Tuba Barut
AU  - Beatrice Zumkehr
AU  - Blandina I. Oliveira Esteves
AU  - Kemal Mehinagic
AU  - Quentin Haas
AU  - Aline Schögler
AU  - Marie-Anne Rameix-Welti
AU  - Jean-François Eléouët
AU  - Ueli Moehrlen
AU  - Thomas M. Marti
AU  - Ralph A. Schmid
AU  - Artur Summerfield
AU  - Horst Posthaus
AU  - Nicolas Ruggli
AU  - Sean R. R. Hall
AU  - Marco P. Alves
TI  - Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection
AID  - 10.1101/2021.05.12.443770
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.12.443770
4099  - http://biorxiv.org/content/early/2021/05/14/2021.05.12.443770.short
4100  - http://biorxiv.org/content/early/2021/05/14/2021.05.12.443770.full
AB  - Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications.AUTHOR SUMMARY This work identifies a novel function of lung-resident MSCs during virus-induced acute lung injury. These findings contribute to the understanding of host response and lung repair mechanisms during a highly prevalent clinical situation and may have therapeutic implications.Competing Interest StatementThe authors have declared no competing interest.