In order to obtain a global picture of how alveolar macrophages respond to influenza A virus (IAV) infection, we used a quantitative proteomics method to systematically examine protein expression in the IAV-infected primary human alveolar macrophages. Of the 1214 proteins identified, 43 were significantly up-regulated and 63 significantly down-regulated at > 95% confidence. The expression of an array of interferon (IFN)-induced proteins was significantly increased in the IAV-infected macrophages. The protein with the greatest expression increase was ISG15, an IFN-induced protein that has been shown to play an important role in antiviral defense. Concomitantly, quantitative real time PCR analysis revealed that the gene expression of type I IFNs increased substantially following virus infection. Our results are consistent with the notion that type I IFNs play a vital role in the response of human alveolar macrophages to IAV infection. In addition to the IFN-mediated responses, inflammatory response, apoptosis and redox state rebalancing appeared also to be major pathways that were affected by IAV infection. Furthermore, our data suggest that alveolar macrophages may play a crucial role in regenerating alveolar epithelium during IAV infection.
【저자키워드】 influenza A virus, LC-MS/MS, quantitative proteomics, protein expression, SILAC, IFN-α/β, primary alveolar macrophage,