| First Author | Li N | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 1 | Pages | 238-43 |
| PubMed ID | 25535343 | Mgi Jnum | J:218162 |
| Mgi Id | MGI:5616938 | Doi | 10.1073/pnas.1414422112 |
| Citation | Li N, et al. (2015) Influenza viral neuraminidase primes bacterial coinfection through TGF-beta-mediated expression of host cell receptors. Proc Natl Acad Sci U S A 112(1):238-43 |
| abstractText | Influenza infection predisposes the host to secondary bacterial pneumonia, which is a major cause of mortality during influenza epidemics. The molecular mechanisms underlying the bacterial coinfection remain elusive. Neuraminidase (NA) of influenza A virus (IAV) enhances bacterial adherence and also activates TGF-beta. Because TGF-beta can up-regulate host adhesion molecules such as fibronectin and integrins for bacterial binding, we hypothesized that activated TGF-beta during IAV infection contributes to secondary bacterial infection by up-regulating these host adhesion molecules. Flow cytometric analyses of a human lung epithelial cell line indicated that the expression of fibronectin and alpha5 integrin was up-regulated after IAV infection or treatment with recombinant NA and was reversed through the inhibition of TGF-beta signaling. IAV-promoted adherence of group A Streptococcus (GAS) and other coinfective pathogens that require fibronectin for binding was prevented significantly by the inhibition of TGF-beta. However, IAV did not promote the adherence of Lactococcus lactis unless this bacterium expressed the fibronectin-binding protein of GAS. Mouse experiments showed that IAV infection enhanced GAS colonization in the lungs of wild-type animals but not in the lungs of mice deficient in TGF-beta signaling. Taken together, these results reveal a previously unrecognized mechanism: IAV NA enhances the expression of cellular adhesins through the activation of TGF-beta, leading to increased bacterial loading in the lungs. Our results suggest that TGF-beta and cellular adhesins may be potential pharmaceutical targets for the prevention of coinfection. |
