Influenza viral neuraminidase primes bacterial coinfection through TGF-beta-mediated expression of host cell receptors----中国科学院微生物研究所

科研成果

论文题目:	Influenza viral neuraminidase primes bacterial coinfection through TGF-beta-mediated expression of host cell receptors
作者:	Li Ning Ren Aihui, Wang Xiaoshuang, Fan Xin, Zhao Yong, Gao George, F., Cleary Patrick, Wang Beinan*.
联系作者:
刊物名称:	Proceedings of the National Academy of Sciences of the United States of America
期:	112
卷:	1
页:	238-243
年份:	2015
影响因子:	10.563
论文下载:	http://www.pnas.org/content/112/1/238.long
摘要:	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 alpha 5 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.