Influenza viral neuraminidase primes bacterial coinfection through TGF-β–mediated expression of host cell receptors

Abstract

Significance Pneumonia caused by bacterial coinfection with influenza virus is the leading cause of mortality in influenza pandemics. TGF-β is known to be activated by influenza virus. In this study we demonstrated that cellular adhesins for bacteria, such as fibronectin and α5 integrin, are up-regulated in influenza viral infection. Inhibition of TGF-β impeded the up-regulation of these cellular adhesins and also influenza viral-enhanced bacterial adherence. In addition, we found that influenza viral-promoted bacterial adherence was dependent on bacterial fibronectin-binding protein. The results indicate that up-regulated expression of cellular adhesins by TGF-β, which is activated in influenza viral infection, increases host susceptibility to bacterial coinfection and suggest that TGF-β and host adhesion molecules are potential pharmaceutical targets for prevention of coinfection.