IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation.
Srikanth SadhuRajdeep DalalJyotsna DandotiyaAkshay BinaykeVirendra SinghManas Ranjan TripathyVinayaka DasSandeep GoswamiShakti KumarZaigham Abbas RizviAmit AwasthiPublished in: Nature communications (2023)
SARS-CoV-2 infection is known for causing broncho-alveolar inflammation. Interleukin 9 (IL-9) induces airway inflammation and bronchial hyper responsiveness in respiratory viral illnesses and allergic inflammation, however, IL-9 has not been assigned a pathologic role in COVID-19. Here we show, in a K18-hACE2 transgenic (ACE2.Tg) mouse model, that IL-9 contributes to and exacerbates viral spread and airway inflammation caused by SARS-CoV-2 infection. ACE2.Tg mice with CD4 + T cell-specific deficiency of the transcription factor Forkhead Box Protein O1 (Foxo1) produce significantly less IL-9 upon SARS-CoV-2 infection than the wild type controls and they are resistant to the severe inflammatory disease that characterises the control mice. Exogenous IL-9 increases airway inflammation in Foxo1-deficient mice, while IL-9 blockade reduces and suppresses airway inflammation in SARS-CoV-2 infection, providing further evidence for a Foxo1-Il-9 mediated Th cell-specific pathway playing a role in COVID-19. Collectively, our study provides mechanistic insight into an important inflammatory pathway in SARS-CoV-2 infection, and thus represents proof of principle for the development of host-directed therapeutics to mitigate disease severity.
Keyphrases
- transcription factor
- respiratory syndrome coronavirus
- sars cov
- coronavirus disease
- oxidative stress
- mouse model
- wild type
- signaling pathway
- squamous cell carcinoma
- small molecule
- pi k akt
- stem cells
- single cell
- binding protein
- dna binding
- locally advanced
- mesenchymal stem cells
- smoking cessation
- amino acid
- genome wide identification