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

Brugger, M.; Demoulins, T.; Barut, G. T.; Zumkehr, B.; Oliveira Esteves, B.; Mehinagic, K.; Haas, Q.; Schogler, A.; Rameix-Welti, M.-A.; Eleouet, J.-F.; Moehrlen, U.; Marti, T.; Schmid, R.; Summerfield, A.; Posthaus, H.; Ruggli, N.; Hall, S.; Alves, M. P.

doi:10.1101/2021.05.12.443770

bioRxiv · 10.1101/2021.05.12.443770

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

Brugger, M.·Demoulins, T.·Barut, G. T.·Zumkehr, B.·Oliveira Esteves, B.·Mehinagic, K.·Haas, Q.·Schogler, A.·Rameix-Welti, M.-A.·Eleouet, J.-F.·Moehrlen, U.·Marti, T.·Schmid, R.·Summerfield, A.·Posthaus, H.·Ruggli, N.·Hall, S.·Alves, M. P.

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Abstract

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 SUMMARYThis 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.

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Brugger, M., Demoulins, T., Barut, G. T., Zumkehr, B., Oliveira Esteves, B., Mehinagic, K., Haas, Q., Schogler, A., Rameix-Welti, M.-A., Eleouet, J.-F., Moehrlen, U., Marti, T., Schmid, R., Summerfield, A., Posthaus, H., Ruggli, N., Hall, S., Alves, M. P.. 2021-05-14. Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection. https://doi.org/10.1101/2021.05.12.443770

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