NF kappa B1 Dichotomously Regulates Pro-Inflammatory and Antiviral Responses in Asthma

Asthma exacerbations are commonly triggered by rhinovirus infections. Viruses can activate the NF kappa B pathway resulting in airway inflammation and increased Th2 cytokine expression. NF kappa B signaling is also involved in early activation of IFN beta, which is a central mediator of antiviral responses to rhinovirus infection. Using a mouse model, this study tests our hypothesis that NF kappa B signaling is involved in impaired IFN beta production at viral-induced asthma exacerbations. C57BL/6 wild-type and NF kappa B1(-/-) mice were challenged with house dust mite for 3 weeks and were subsequently stimulated with the rhinoviral mimic poly(I:C). General lung inflammatory parameters and levels of the Th2 upstream cytokine IL-33 were measured after allergen challenge. At exacerbation, production of IFN beta and antiviral proteins as well as gene expression of pattern recognition receptors and IRF3/IRF7 was assessed. In the asthma exacerbation mouse model, lack of NF kappa B1 resulted in lower levels of IL-33 after allergen challenge alone and was associated with reduced eosinophilia. At exacerbation, mice deficient in NF kappa B1 exhibited enhanced expression of IFN beta and antiviral proteins. This was accompanied by increased IRF3/IRF7 expression and induction of pattern recognition receptor expression. In a human asthma dataset, a negative correlation between IRF3 and NF kappa B1 expression was observed. NF kappa B may impair antiviral responses at exacerbation, possibly by reducing expression of the transcription factors IRF3/IRF7. These findings suggest a therapeutic potential for targeting NF kappa B pathways at viral infection-induced exacerbations.