In clinical scenarios, a variety of pathogens are involved in lung infections. In particular, viral infections are a significant risk factor for acquiring bacterial infections4344. TLR3 is thought to be a major mediator of the cellular response to viral infection, because it responds to dsRNA, a common by-product of viral replication45. TLR3 has been implicated in infections by mouse cytomegalovirus (MCMV), reoviruses, lymphocytic choriomeningitis virus (LCMV), and influenza A virus (IAV)9. TLR3−/− mice are more resistant to lethal West Nile virus, a mosquito-borne ssRNA flavivirus, which causes human disease of variable severity46, and show reduced inflammation and lethality upon IAV infection4748. Thus, up-regulation of TLR3 may contribute to an increased lung immune response to viral infection following a bacterial infection. Despite the relatively well-known role of viral infections in promoting bacterial infections, it is still not clear whether bacterial infections also promote viral infections. Therefore, our results are the first to offer new insight into this topic. There is also a growing body of evidence showing that most patients have a mixture of bacterial and viral infection4950, and the cross talk between TLR4 and TLR3 induces a synergistic inflammatory response in cases of mixed infection. Cameron R.J. et al.49 found that bacterial and viral pathogens interact to cause additional increases in inflammatory markers and an exacerbation of disease severity in patients with chronic obstructive pulmonary disease (COPD). TLR3 has been shown to respond to dsRNA, a replication intermediary for many viruses, but the heterologous RNA released from necrotic cells or that is generated by in vitro transcription, such as mRNA, also stimulates TLR3 signaling and induces immune activation. Indeed, Cavassani KA15 observed TLR3 activation during experimental polymicrobial sepsis and ischemia gut injury in the absence of an exogenous viral stimulus, and TLR3−/− mice were protected from the lethal effects of sustained inflammation. Moreover, treatment with a TLR3 antibody could attenuate the tissue injury associated with gut ischemia and significantly decrease sepsis-induced mortality. Therefore, TLR3 serves as a regulator of the amplification of the immune response as well as an endogenous sensor of necrosis, independent of viral activation. Our study showed that up-regulation of TLR3 significantly amplified IL-6, TNF-α, MCP-1, and MIP-2 expression, which then enhanced PMN migration and finally led to ALI.