Alveolar macrophages produce a robust innate immune response to influenza. This includes a significant induction of cytokines and chemokines, pathogen recognition, and apoptotic responses, which are similar to the responses of human monocyte derived macrophages [16, 17] . Consistent with other studies of avian or human influenza infections in humans and animals [16, 17, [31] [32] [33] , PR/8 stimulated an early and prominent IFN response in human AM despite of the failure to release infectious viral particles. Human AM produce both type I and type III interferons (Figures 1 and 2) . In contrast, alveolar epithelial cells do not produce any type I interferon IFN-a in response to influenza [34] . These results indicate a cell-specific pattern in producing IFN in response to viral infection. It is well known that RIG-I like RNA helicases (RLHs) and TLRs are the two main PRRs responsible for IFN production against RNA viruses including influenza. RLHs (RIG-I and MDA-5) recognize cytoplasmic viral double-stranded RNA, whereas TLRs (TLR3 and TLR7) sense viral nucleic acid in the endosomal compartment [35, 36] . In the current study, PR/8 infection up-regulated mRNA levels of RIG-I and MDA-5 mainly at 4 hpi, but the mRNAs of TLR3 and 7 mainly at 24 hpi ( Figure 1B) , which suggests that RLHs might be the early sensors and TLRs might be the late sensors for PR/8 in human AM. These results correlate well with those reported by Takeuchi and Thompson that RLHs were responsible for local production of IFNs, whereas TLRs were mainly involved in the late stages of systemic infection [35, 36] . At early times PR/8 triggered mainly pro-inflammatory responses, whereas at later times PR/8 also activated pathways involved in the maintenance of homeostasis such as the activation of IL-10 and IL-6, as well as up-regulation of SOCS genes (Data S1). Therefore, therapeutic regulation of the inflammatory response in acute lung injury should consider both strategies to inhibit secreted cytokines but also strategies to dampen the innate immune response by stimulating IL-10 and SOCS genes. We were able to confirm the results found with PR/8 in contemporary influenza virus NY/238-infected human AM with the exception of an increase in TLR7 mRNA. This might be due to a lower MOI of virus used in the experiments because of the limitation of the viral titer, but it could also be due to differences in the natures of these two viruses or the difference in methods for propagating these two viruses.