69 : Interferon-lambda is produced by and induces autocrine expression of interferon-stimulated genes in human bronchial epithelial cells

详细信息    查看全文

• 作者：Harold Dickensheets ; Faruk Sheikh ; Rachel Shepard ; Philippa Hillyer ; Ronald L. Rabin ; Raymond P. Donnelly
• 刊名：Cytokine
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：63
• 期：3
• 页码：259
• 全文大小：45 K

文摘

Interferons play a key role in the innate immune response to viral infection. In this study, we determined which IFN genes are expressed by primary human bronchial epithelial (HBE) cells following infection with respiratory syncytial virus (RSV) strain A2. Infection of HBE cells with RSV induced co-expression of the IFN-lambda genes (IFNL1, IFNL2 andIFNL3) in a dose- and time-dependent manner. It also induced expression of the IFNB1 gene and low levels of the IFNA1 gene but not other type-I IFN genes. Induction of IFNB1 andIFNL gene expression correlated with marked increases in the levels of IFN-¦Â and IFN-¦Ë protein in the culture supernatants. The newly expressed IFN-¦Â and IFN-¦Ë proteins in turn induced activation of STAT1 and STAT2 and subsequent expression of mulitple IFN-stimulated genes (ISGs), including MX1, OAS1, IFIT1, IFIT3, IFI44 andIRF7. Using neutralizing antibodies that selectively inhibit the activity of type-I versus type-III IFNs, we determined that ISG expression induced by RSV infection in HBE cells can be inhibited partially by either anti-type I or anti-type III IFN antibodies and almost completely by co-treatment with both types of antibodies together. Recombinant human IFN-¦Ë1 induced activation of STAT1 and STAT2 in na?ve HBE cells, and induced expression of the same ISGs that were induced by viral infection. Furthermore, pre-treatment with recombinant human IFN-¦Ë1 decreased the ability of RSV to infect na?ve HBE cells indicating that IFN-¦Ë1 may be a useful prophylactic agent to protect against infection by respiratory viruses that preferentially infect airway epithelial cells. These findings demonstrate that bronchial epithelial cells express significant levels of both type I and type III IFN following viral infection. Furthermore, the newly expressed IFN-¦Â and IFN-¦Ë proteins combine to mobilize a potent antiviral response in HBE cells by inducing autocrine expression of multiple ISGs.