Open AccessPulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection
Author(s) -
Melanie Brügger,
Thomas Démoulins,
G. Tuba Barut,
Béatrice Zumkehr,
Blandina I. Oliveira Esteves,
Kemal Mehinagic,
Quentin Haas,
Aline Schögler,
MarieAnne RameixWelti,
Jean François Eléouët,
Ueli Moehrlen,
Thomas Marti,
Ralph A. Schmid,
Artur Summerfield,
Horst Posthaus,
Nicolas Ruggli,
Sean Hall,
Marco P. Alves
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009789
Subject(s) - mesenchymal stem cell , virus , immunology , biology , lung , stem cell , respiratory system , virology , cancer research , medicine , microbiology and biotechnology , anatomy
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.