Background We studied the contribution of Duox2 in mucosal host defense against influenza A virus (IAV) infection in vivo lung. We found that Duox2 was required for the induction of type I and III interferon (IFN)s and transient Duox2 overexpression lead to suppress IAV infection in vivo lung.
Methods 20 Mice (C57BL/6J) were anesthetized and challenged by intranasal administration of 213 pfu/30 ul of IAV (WS/33/H1N1) and IAV-infected mice were euthanized at 1, 3, 5, 7, 10, 14 days post of infection (dpi). Duox2 shRNA and pCMV-Duox2 were inoculated to mice to assess the regulatory mechanism between Duox2 and IFN secretion.
Results Following intranasal IAV inoculation, viral infection was significantly aggravated from 3 dpi in vivo lung and viral titer was highest at 7 dpi. Consistent with this, Duox2 mRNA and protein expressions were significantly induced from 3 dpi in the lung tissue of IAV-infected mice. Viral titer was much higher in IAV-infected mice that were inoculated with Duox2 shRNA accompanied with lower survival rate and extensive lung pathologies. Interestingly, severe lung pathologies in IAV-infected mice were not observed and viral titer was significantly reduced in mice with pulmonary administration of pCMV-Duox2 before IAV inoculation. Both mRNA and secreted protein levels of IFN-β and IFN-λ2/3 were highly elevated in IAV-infected mice with pCMV-Duox2.
Conclusion Duox2 is necessary for the regulation of IFNs secretion in vivo lung and pulmonary administration of Duox2 DNA trigger the induction of type I and III IFNs resulting in more complete suppression of IAV infection.