Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb;54(2):109-119.
doi: 10.1111/cea.14425. Epub 2023 Nov 27.

Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection

Kunyuan Tian  1 , Prakrati Dangarh  2 , Haina Zhang  1 , Christian L Hines  2 , Andrew Bush  1   3 , Hannah J Pybus  2 , James A Harker  1 , Clare M Lloyd  1 , Reiko J Tanaka  2 , Sejal Saglani  1   3
Affiliations

Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection

Kunyuan Tian et al. Clin Exp Allergy. 2024 Feb.

Abstract

Background: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain.

Methods: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity.

Results: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4+ IL-13+ and CD4+ IL-5+ cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised.

Conclusions: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.

Keywords: in silico modelling; neonatal murine model; pre-school wheeze; recurrent viral infections; respiratory syncytial virus.

PubMed Disclaimer

References

REFERENCES

    1. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The group health medical associates. N Engl J Med. 1995;332(3):133-138.
    1. Kotaniemi-Syrjanen A, Reijonen TM, Korhonen K, Korppi M. Wheezing requiring hospitalization in early childhood: predictive factors for asthma in a six-year follow-up. Pediatr Allergy Immunol. 2002;13(6):418-425.
    1. Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B, Björkstén B. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics. 1995;95(4):500-505.
    1. Saglani S. Viral infections and the development of asthma in children. Ther Adv Infect Dis. 2013;1(4):139-150.
    1. Sigurs N, Aljassim F, Kjellman B, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax. 2010;65(12):1045-1052.

Publication types