Furthermore, poly I:C pre-exposure led to increased mortality rates following secondary bacterial challenge, which appeared to be the result of a steadily rising lung and blood bacterial burden. The mechanism responsible for poly I:C-mediated impairment was dependent upon type I IFNs, as animals deficient in the common type I interferon receptor, Ifnar2/2 mice, did not display the same magnitude of impaired bacterial clearance as WT following poly I:C pre-exposure. Whether type I IFN alone is GDC-0879 sufficient to cause suppression against bacterial infection, or whether type I IFN is deleterious in the context of the immune dysregulation created by activation of “antiviral” immune responses remains to be determined. Patients treated with chronic IFN therapy often develop neutropenia and bone marrow suppression, which is the most frequent reason for dose reduction or cessation of the drug. Approximately 18–22% of subjects on interferon therapy will develop infectious complications. Interestingly, in these studies, infections were not necessarily associated with neutropenia, raising the possibility that chronic interferon therapy may have other detrimental effects on the immune system. In our model, we observe a relatively modest impairment of neutrophil recruitment in poly I:C treated WT versus Ifnar2/2 animals; however, at this timepoint, the wildtype animals already have markedly increased bacterial numbers. Therefore, in the poly I:C model, type I IFNs may have additional effects on immune cell function beyond their effects on inflammatory cell recruitment. In contrast, administration of comparably high or higher doses of the TLR7 agonists, imiquimod or gardiquimod, was not sufficient to suppress antibacterial host defense. We observed that the dose of gardiquimod used for intranasal challenge was not sufficient to induce significant levels of type I IFNs in the lung, supporting the notion that induction of type I IFNs is necessary for post-viral inhibition of bacterial clearance. This may be in part due to the fact that TLR7 expression is largely limited to plasmacytoid dendritic cells, whereas TLR3 expression is constitutive in the lung and more widespread, including pulmonary epithelial cells and macrophages. However, if higher doses of TLR7 were used or TLR7 expression were upregulated, perhaps significant amounts of type I IFN would be elaborated which may contribute to impaired bacterial clearance. Furthermore, systemic administration of TLR7 ligands have been demonstrated to reduce the number of circulating leukocytes, suggesting that activation of the TLR7 pathway may have other detrimental effects on antibacterial immunity. Although in our system we failed to demonstrate a role for TLR7 activation in inducing susceptibility to bacterial pneumonia, further studies are needed to determine whether TLR7 signaling during actual influenza and other viral infections contributes towards impaired pulmonary antibacterial defense. Viral infections have multiple effects on the host, including activation of multiple immune pathways and induction of tissue injury, which may contribute to the dysregulated immune response during secondary infections. Although poly I:C may not completely recapitulate the effects of viral infection on pulmonary host defense, we believe that our study illustrates the utility of using poly I:C as a model for viral-induced immunosuppression. Since poly I:C mimics the immune responses of viruses that either have dsRNA genomes or which undergo a dsRNA stage during replication, this model may potentially aid in the identification of molecules that would be possible candidates for “universal” mediators of postviral immunosuppression.