tetano
Editor, Senior Moderator
Respirology
. 2021 Sep 1.
doi: 10.1111/resp.14141. Online ahead of print.
IL-17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus
Xiaoming Liu[SUP] 1 2 [/SUP], Thi Hiep Nguyen[SUP] 1 2 [/SUP], Leon Sokulsky[SUP] 1 [/SUP], Xiang Li[SUP] 1 2 [/SUP], Keilah Garcia Netto[SUP] 1 2 [/SUP], Alan Chen-Yu Hsu[SUP] 2 3 4 [/SUP], Chi Liu[SUP] 5 [/SUP], Karen Laurie[SUP] 6 [/SUP], Ian Barr[SUP] 6 [/SUP], Hock Tay[SUP] 1 2 [/SUP], Fiona Eyers[SUP] 1 2 [/SUP], Paul S Foster[SUP] 1 2 [/SUP], Ming Yang[SUP] 1 2 [/SUP]
Affiliations
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.
Keywords: IL-17A; airway inflammation; immunopathology; influenza virus; respiratory virus; rhinovirus and respiratory syncytial virus; viral infection.
. 2021 Sep 1.
doi: 10.1111/resp.14141. Online ahead of print.
IL-17A is a common and critical driver of impaired lung function and immunopathology induced by influenza virus, rhinovirus and respiratory syncytial virus
Xiaoming Liu[SUP] 1 2 [/SUP], Thi Hiep Nguyen[SUP] 1 2 [/SUP], Leon Sokulsky[SUP] 1 [/SUP], Xiang Li[SUP] 1 2 [/SUP], Keilah Garcia Netto[SUP] 1 2 [/SUP], Alan Chen-Yu Hsu[SUP] 2 3 4 [/SUP], Chi Liu[SUP] 5 [/SUP], Karen Laurie[SUP] 6 [/SUP], Ian Barr[SUP] 6 [/SUP], Hock Tay[SUP] 1 2 [/SUP], Fiona Eyers[SUP] 1 2 [/SUP], Paul S Foster[SUP] 1 2 [/SUP], Ming Yang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34472161
- DOI: 10.1111/resp.14141
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.
Keywords: IL-17A; airway inflammation; immunopathology; influenza virus; respiratory virus; rhinovirus and respiratory syncytial virus; viral infection.