Influenza A virus-induced inflammasome activation is dependent on P2X 7 receptor and src tyrosine kinase activity Several proteins related with inflammatory response were identified from influenza A virus-infected macrophages. Thus, we created a network based on known protein-protein interactions between all the inflammation-related proteins identified from the intracellular fractions of the infected cells (Fig. 5A) . NLPR3 was added to our protein interaction network since it has been shown to be essential for the activation of inflammatory response during influenza A virus infection. Protein interaction network showed that purinenergic P2X 7 receptor is directly linked to NLRP3. P2X 7 receptor has been shown to be involved in NLRP3 activation in response to extracellular ATP [21, 22] , and host tissue damage during influenza A virus infection may result in extracellular leakage of ATP. Therefore we studied the role P2X 7 receptor in virus-induced inflammasome activation. Specific inhibitor for P2X 7 receptor, AZ11645373, clearly diminished IL-18 secretion in infected macrophages (Fig. 5B ). In addition to IL-18, NLRP3 inflammasome regulates the secretion of IL-1b. We have previously shown that influenza A virus infection is not able to induce production of proIL-1b in human macrophages [23] . Therefore we stimulated macrophages with LPS for 18 h to activate proIL-1b production, after which the macrophages were infected with influenza A virus for 9 h in the presence and absence of AZ11645373. This P2X 7 receptor inhibitor almost completely abrogated influenza A virus-induced IL-1b secretion (Fig. 5C ). In addition to pharmacological inhibition, we used small interfering (si)RNA approach to study the role of P2X 7 receptor in influenza A virus-induced inflammasome activation. Human macrophages were treated with control siRNA and P2X 7 receptor specific siRNAs for 24 h after which the cells were left unstimulated or infected with influenza A virus for 9 h. Silencing of P2X 7 receptor clearly reduced influenza A virus-induced IL-18 secretion (Fig. 5D) and Western blot analysis confirmed that P2X 7 receptor protein expression was decreased in P2X 7 receptor siRNA-treated macrophages (Fig. 5E ). In conclusion, our results show that P2X7 receptor is essential for influenza A virus-induced inflammasome activation.