In conclusion, our high-throughput, unbiased quantitative proteomics study provides important new insight into hostresponse against influenza A virus infection in human primary macrophages (Fig. 6) . First, our data shows that there are dramatic changes in mitochondrial and nuclear proteomes in response to infection. Secondly, our data demonstrates that there is rapid cytoplasmic leakage of lysosomal proteins, including cathepsins, upon infection which contributes to inflammasome activation and apoptosis seen in infected macrophages. Thirdly, our data demonstrates that P2X 7 receptor and src tyrosine kinase activity are essential for inflammasome activation during influenza A virus infection. Finally, we show that influenza A virus infection is associated with robust secretion of different DAMPs suggesting an important role for DAMPs in antiviral response.