tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2014 Dec 22. pii: 201414422. [Epub ahead of print]
[h=1]Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors.[/h] Li N[SUP]1[/SUP], Ren A[SUP]1[/SUP], Wang X[SUP]1[/SUP], Fan X[SUP]1[/SUP], Zhao Y[SUP]2[/SUP], Gao GF[SUP]1[/SUP], Cleary P[SUP]3[/SUP], Wang B[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-β. Because TGF-β can up-regulate host adhesion molecules such as fibronectin and integrins for bacterial binding, we hypothesized that activated TGF-β 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 α5 integrin was up-regulated after IAV infection or treatment with recombinant NA and was reversed through the inhibition of TGF-β 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-β. 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-β signaling. Taken together, these results reveal a previously unrecognized mechanism: IAV NA enhances the expression of cellular adhesins through the activation of TGF-β, leading to increased bacterial loading in the lungs. Our results suggest that TGF-β and cellular adhesins may be potential pharmaceutical targets for the prevention of coinfection.
[h=4]KEYWORDS:[/h] TGF-beta; bacterial adherence; coinfection; fibronectin binding protein; influenza A virus
PMID: 25535343 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25535343
[h=1]Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors.[/h] Li N[SUP]1[/SUP], Ren A[SUP]1[/SUP], Wang X[SUP]1[/SUP], Fan X[SUP]1[/SUP], Zhao Y[SUP]2[/SUP], Gao GF[SUP]1[/SUP], Cleary P[SUP]3[/SUP], Wang B[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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-β. Because TGF-β can up-regulate host adhesion molecules such as fibronectin and integrins for bacterial binding, we hypothesized that activated TGF-β 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 α5 integrin was up-regulated after IAV infection or treatment with recombinant NA and was reversed through the inhibition of TGF-β 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-β. 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-β signaling. Taken together, these results reveal a previously unrecognized mechanism: IAV NA enhances the expression of cellular adhesins through the activation of TGF-β, leading to increased bacterial loading in the lungs. Our results suggest that TGF-β and cellular adhesins may be potential pharmaceutical targets for the prevention of coinfection.
[h=4]KEYWORDS:[/h] TGF-beta; bacterial adherence; coinfection; fibronectin binding protein; influenza A virus
PMID: 25535343 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25535343