The MSC–RSV/HMPV interface: impacts on pulmonary homeostasis, remodeling, and risk of non-atopic asthma and COPD

Respiratory tract infections continue to represent a major cause of pediatric morbidity and mortality. Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (HMPV) are highlighted as key etiologic agents of bronchiolitis and pneumonia, particularly in children under two years old. Recurrent infections during the second year of life may be associated with significant histopathological damage and might also be a risk factor for developing chronic pulmonary diseases, such as non-atopic asthma. In adults, these viruses similarly elevate clinical burden on the elderly and individuals with Chronic Obstructive Pulmonary Disease (COPD), causing the exacerbation of respiratory signals and symptoms and, consequently, promoting a chronic inflammatory response that modifies the lung tissue and disease progression. Tissue repair and the homeostasis recovery might be associated with the participation of Mesenchymal Stem Cells (MSCs), both lung resident and migratory MSCs, these cells are characterized by their plasticity and immunomodulatory capacity, which are relevant to restoring tissue homeostasis after injury. However, RSV and HMPV may also infect MSCs, raising the question that infected MSCs could lose immunomodulatory efficacy and plasticity, thereby affecting tissue renewal. This review aims to provide an overview of the effect of respiratory viral infections, their implications in the lung tissue damage and the possible participation of MSCs in the recovery of lung homeostasis by tissue repair and immune response modulation.