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Updated: Aug 9, 2025
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
IL-17A plays a critical role in RSV infection in children and mice
Xin Long1,2, Jun Xie1,2, Luo Ren1,2
1Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, No.136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People's Republic of China.
Insights
Interleukin-17A (IL-17A) exacerbates respiratory syncytial virus (RSV) infection in children and mice, leading to airway dysfunction. Targeting IL-17A may offer therapeutic benefits for severe RSV cases.
Area of Science:
- Immunology
- Respiratory Medicine
- Virology
Background:
- Interleukin-17A (IL-17A) is linked to asthma, but its role in respiratory syncytial virus (RSV) infection remains unclear.
- Conflicting data exists regarding IL-17A's involvement in RSV pathogenesis.
Purpose of the Study:
- To investigate the role of IL-17A in RSV infection and associated airway dysfunction.
- To explore the cellular sources and regulatory pathways of IL-17A in RSV infection.
Main Methods:
- Clinical analysis of RSV-infected children's nasopharyngeal aspirates for cytokine levels.
- Murine model of RSV infection using wild-type and IL-17A knockout mice.
- Assessment of bronchoalveolar lavage fluid, lung histopathology, airway hyperresponsiveness, and specific immune cell populations.
Main Results:
- IL-17A levels were elevated in RSV-infected children and correlated with pneumonia severity.
- RSV infection increased IL-17A in murine models, and its neutralization or absence alleviated airway inflammation, lung damage, and hyperresponsiveness.
- IL-17A production was modulated by CD4+ T cells (decreasing) and CD8+ T cells (increasing), with parallel increases in IL-6, IL-21, IL-23R, and RORγt.
Conclusions:
- IL-17A exacerbates RSV-induced airway dysfunction in both pediatric and murine models.
- CD4+ T cells are identified as the primary source of IL-17A during RSV infection.
- The IL-6/IL-21-IL-23R-RORγt signaling pathway may play a role in regulating IL-17A production in RSV.
Background:
IL-17A is a pleiotropic cytokine and intimately associated with asthma, but its role in respiratory syncytial virus (RSV) infection is conflicting in the literature.
Methods:
Children hospitalized in the respiratory department with RSV infection during RSV pandemic season of 2018-2020 were included. Nasopharyngeal aspirates were collected for pathogen and cytokines determination. In the murine model, RSV intranasal administrations were performed in wild-type and IL-17A-/- mice. Leukocytes and cytokines in bronchoalveolar lavage fluid (BALF), lung histopathology, and airway hyperresponsiveness (AHR) were measured. RORγt mRNA and IL-23R mRNA were semi-quantified by qPCR.
Results:
IL-17A increased significantly in RSV-infected children and was positively associated with pneumonia severity. In the murine model, IL-17A significantly increased in BALF of mice with RSV infection. Airway inflammation, lung tissue damage and AHR were significantly alleviated in wild-type mice following IL-17A neutralization and in the IL-17A-/- mice. IL-17A decreased by removing CD4+ T cells but increased by depleting CD8+ T cells. IL-6, IL-21, RORγt mRNA and IL-23R mRNA dramatically increased in parallel with the rise of IL-17A.
Conclusions:
IL-17A contributes to the airway dysfunctions induced by RSV in children and murine. CD3+CD4+T cells are its major cellular sources and the IL-6/IL-21-IL-23R-RORγt signaling pathway might participate in its regulation.
