Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection.

Brügger, Melanie; Démoulins, Thomas; Barut, G. Tuba; Zumkehr, Beatrice; Oliveira Esteves, Blandina I.; Mehinagic, Kemal; Haas, Quentin; Schögler, Aline; Rameix-Welti, Marie-Anne; Eléouët, Jean-François; Moehrlen, Ueli; Marti, Thomas M.; Schmid, Ralph A.; Summerfield, Artur; Posthaus, Horst; Ruggli, Nicolas; Hall, Sean R. R.; Alves, Marco P. (2021). Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection. PLoS pathogens, 17(7), e1009789. Public Library of Science 10.1371/journal.ppat.1009789

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Brügger, Melanie; Démoulins, Thomas Paul Rémi; Barut, G Tuba; Zumkehr, Béatrice; Oliveira Esteves Criblez, Blandina Isabel; Haas, Quentin; Marti, Thomas; Schmid, Ralph; Summerfield, Artur; Posthaus, Horst; Ruggli, Nicolas; Hall, Sean and Alves, Marco

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health

ISSN:

1553-7366

Publisher:

Public Library of Science

Language:

English

Submitter:

Andrea Stettler

Date Deposited:

03 Sep 2021 14:14

Last Modified:

05 Sep 2021 03:05

Publisher DOI:

10.1371/journal.ppat.1009789

PubMed ID:

34320038

BORIS DOI:

10.48350/159173

URI:

https://boris.unibe.ch/id/eprint/159173

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