Journal
PLOS PATHOGENS
Volume 17, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1009789
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Funding
- Swiss National Science Foundation [310030_172895]
- Gottfried and Julia Bangerter-Rhyner Foundation
- Swiss National Science Foundation (SNF) [310030_172895] Funding Source: Swiss National Science Foundation (SNF)
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The research highlights the critical role of lung-resident MSCs in virus-induced acute lung injury, showing their involvement in immune response, repair mechanisms, and expansion of the pulmonary MSC pool following infection. These findings contribute to a better understanding of host response and lung repair mechanisms, with potential therapeutic implications.
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.
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