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

Démoulins, Thomas; Brügger, Melanie; Zumkehr, Beatrice; Oliveira Esteves, Blandina I; Mehinagic, Kemal; Fahmi, Amal; Borcard, Loïc; Taddeo, Adriano; Jandrasits, Damian; Posthaus, Horst; Benarafa, Charaf; Ruggli, Nicolas; Alves, Marco P (2021). The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis. PLoS pathogens, 17(4), e1009529. Public Library of Science 10.1371/journal.ppat.1009529

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Demoulins, Thomas; Brügger, Melanie; Zumkehr, Béatrice; Oliveira Esteves Criblez, Blandina Isabel; Mehinagic, Kemal; Fahmi, Amal; Borcard, Loïc Vivien; Taddeo, Adriano; Jandrasits, Damian; Posthaus, Horst; Benarafa, Charaf; Ruggli, Nicolas and Alves, Marco

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1553-7366

Publisher:

Public Library of Science

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

13 Jul 2021 09:28

Last Modified:

18 Jul 2021 03:06

Publisher DOI:

10.1371/journal.ppat.1009529

PubMed ID:

33909707

BORIS DOI:

10.48350/156610

URI:

https://boris.unibe.ch/id/eprint/156610

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