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.
Highlights
The ability of organs to maintain homeostasis and regenerate following injury is vital to an organism
This work identifies a novel function of lung-resident mesenchymal stem and stromal cells (MSCs) during virus-induced acute lung injury
To study the immunobiology of LR-MSCs during respiratory virus infection, we determined first if these cells are susceptible towards respiratory syncytial virus (RSV) infection in comparison to a well described cellular target of RSV, namely airway epithelial cells (AECs) [21,22,23]
Summary
The ability of organs to maintain homeostasis and regenerate following injury is vital to an organism. MSCs are found in nearly every vascularized tissue including the upper and lower respiratory tract They are localized in perivascular niches of small and larger blood vessels and were shown to be lung-resident [1,2,3,4,5,6,7]. Lung-resident (LR)-MSCs can interact with epithelial cells and promote alveolar cell growth, differentiation, and self-renewal. This is of particular importance for epithelial maintenance as well as for repair and regeneration as demonstrated in artificial rodent models of lung injury [8,9,10]. Characterization of immunomodulatory properties of mesenchymal cells are of great clinical importance since non-resident MSCs are the subject of cell-based treatment approaches for various lung disorders [14,15]
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