The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis.

• Main Authors: Thomas Démoulins, Melanie Brügger, Beatrice Zumkehr, Blandina I Oliveira Esteves, Kemal Mehinagic, Amal Fahmi, Loïc Borcard, Adriano Taddeo, Damian Jandrasits, Horst Posthaus, Charaf Benarafa, Nicolas Ruggli, Marco P Alves
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2021-04-01
• Series: PLoS Pathogens
• Online Access: https://doi.org/10.1371/journal.ppat.1009529

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4+ and CD8+ T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.