Article ; Online: IL-17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus.
2021 Volume 26, Issue 11, Page(s) 1049–1059
Abstract: Background and objective: Influenza virus (FLU), rhinovirus (RV) and respiratory syncytial virus (RSV) are the most common acute respiratory infections worldwide. Infection can cause severe health outcomes, while therapeutic options are limited, ... ...
| Abstract | Background and objective: Influenza virus (FLU), rhinovirus (RV) and respiratory syncytial virus (RSV) are the most common acute respiratory infections worldwide. Infection can cause severe health outcomes, while therapeutic options are limited, primarily relieving symptoms without attenuating the development of lesions or impaired lung function. We therefore examined the inflammatory response to these infections with the intent to identify common components that are critical drivers of immunopathogenesis and thus represent potential therapeutic targets. Methods: BALB/c mice were infected with FLU, RV or RSV, and lung function, airway inflammation and immunohistopathology were measured over a 10-day period. Anti-IL-17A mAb was administered to determine the impact of attenuating this cytokine's function on the development and severity of disease. Results: All three viruses induced severe airway constriction and inflammation at 2 days post-infection (dpi). However, only FLU induced prolonged inflammation till 10 dpi. Increased IL-17A expression was correlated with the alterations in lung function and its persistence. Neutralization of IL-17A did not affect the viral replication but led to the resolution of airway hyperresponsiveness. Furthermore, anti-IL-17A treatment resulted in reduced infiltration of neutrophils (in RV- and FLU-infected mice at 2 dpi) and lymphocytes (in RSV-infected mice at 2 dpi and FLU-infected mice at 10 dpi), and attenuated the severity of immunopathology. Conclusion: IL-17A is a common pathogenic molecule regulating disease induced by three prevalent respiratory viruses. Targeting the IL-17A pathway may provide a unified approach to the treatment of these respiratory infections alleviating both inflammation-induced lesions and difficulties in breathing. |
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| MeSH term(s) | Animals ; Interleukin-17/immunology ; Lung/physiopathology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae ; Orthomyxoviridae Infections/immunology ; Picornaviridae Infections/immunology ; Respiratory Syncytial Virus Infections ; Respiratory Syncytial Viruses/immunology ; Rhinovirus |
| Chemical Substances | Interleukin-17 |
| Language | English |
| Publishing date | 2021-09-01 |
| Publishing country | Australia |
| Document type | Journal Article |
| ZDB-ID | 1435849-9 |
| ISSN | 1440-1843 ; 1323-7799 |
| ISSN (online) | 1440-1843 |
| ISSN | 1323-7799 |
| DOI | 10.1111/resp.14141 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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