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

Abstract

Rationale: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infancy, potentially aided by an inappropriate immune response. Sparse information is available for the distal lung, mostly because data arose from non-invasive samplings of peripheral blood and nasal aspirates. Objectives: To determine the neonatal immune response to RSV in the bronchoalveolar space and better understand why neonates are at greater risk of developing severe disease. Methods: We used the newborn lamb, a state-of-the-art translational model of human RSV infection, offering ease sampling and full accessibility to lower airways. Using a multiparameter flow cytometry assay, we evaluated the frequency and activation/maturation state of the major subsets of the developing T-cell compartment. Measurements and Main Results: The T-cell compartment of the healthy developing lung was very distinct to that seen in adults. We observed a high frequency of type 2 CD4+ (Th2) and CD8+ (Tc2) T-cells, both being a large source of IL-4, which declined progressively over time. Remarkably, RSV infection exacerbated this pro-type 2 environment, rather than inducing a type 2 response per se. Neonatal regulatory T-cell (Treg) suppressive functions occurred very early to dampen those Th2 and Tc2 responses, while γδ T-cells dropped and failed to produce IL-17. The disease severity was related to the magnitude of these T-cell responses. Conclusion: The atypical neonatal immune response to RSV consists of distinct T-cell subsets that tightly cooperate, namely a combined bronchoalveolar influx of Treg, Th2 and Tc2 cells, associated with a depletion of γδ T-cells.

Evaluation of Newborns with Non-COVID-19 Pneumonia Hospitalized in the Neonatal Intensive Care Unit during the COVID-19 Pandemic, Turkey, Izmir 2020–2021

“…RSV infections with severe course require hospitalization in NICU; T helper 2 promotes immune response. 16 The decrease in natural killer (NK) cells due to RSV further increases the clinical severity of infection. In addition, infected NK cells tend to produce interferon-gamma.…”