hours. Differential BAL cell counts showed no changes in macrophage numbers between the mouse strains. These data indicate that JNK1 is required for the normal immune response to the gram-negative bacteria E. coli. Deletion of JNK1 resulted in decreased lung inflammation and increased pathogen burden. E. coli, and other gram-negative bacteria, drives inflammation through interaction of LPS with the Tlr4 signaling cascade. Gram-positive bacteria initiate inflammation largely through interactions with Tlr2 and other pathways. To test whether JNK1 plays a role in host Piceatannol web defense against gram-positive bacteria, we challenged WT and JNK1 2/2 mice with S. aureus. JNK1 2/ 2 mice did not have significantly elevated S. aureus burden one day after challenge. Similar to the E. coli challenge model, JNK1 2/2 and WT mice had similar BAL cell numbers, but JNK1 2/2 mice recruited significantly less macrophages. Deletion of JNK1 resulted in significantly less IL-1a production, but did not impact other cytokines that were decreased in 
the gram-negative model. These data suggest that JNK1 does not play a large role in host defense or inflammation in response to the gram positive bacterium S. aureus. JNK1 modulates the pathophysiology of Influenza A infection Studies presented thus far addressed the role of JNK1 in host defense against extracellular pathogens. Next, the role of JNK1 in intracellular host defense was evaluated. WT and JNK1 2/2 mice were infected with Influenza A PR/8/34 H1N1 for seven days. JNK1 2/2 mice displayed increased weight loss throughout the infection time course compared to WT mice. Interestingly, despite having greater morbidity as measured by weight loss, JNK1 2/2 mice had decreased viral burden versus WT mice on day seven. The total number of BAL inflammatory cells was unaltered in JNK1 2/2 mice, however, these mice had significantly decreased macrophage recruitment 3 JNK1 and Host Defense and increased lymphocyte numbers compared to control mice. One possible explanation for increased morbidity would be an enhanced inflammatory profile or cytokine storm in JNK1 2/2 mice. Analysis of tissue inflammation by histopathology revealed no differences in parenchymal or peribronchial inflammation. Consistent with the small changes in inflammation observed, JNK1 2/2 mice had significantly reduced KC and IL-10 production, but many cytokines were unaffected versus WT ” mice. IL-23p19 production trended towards decreased production in JNK1 2/2 compared to WT mice. Overall, these data show that JNK1 plays a minor role in lung inflammation induced by Influenza A, but is critical to determining morbidity and viral burden. One potentially key difference observed in JNK1 2/2 mice by histopathology was the presence of plugging of airways. This phenotype was not observed in any sections from WT mice. To determine if the airway plugging was perhaps due to mucus hyper-production, expression of Muc5ac, Muc5b, and Clca3 were examined. JNK1 2/2 mice did not display different levels of mucin gene expression versus WT mice. In addition, neither WT nor JNK1 2/2 mice stained positive for mucus hyper-production by Periodic Acid Schiff staining. Finally, the mechanism by which JNK1 2/2 mice have lower Influenza A burden was investigated. The type I interferon response has been shown to be critical to improving viral host defense and clearance. WT and JNK1 2/2 mice produced similar ” levels of IFNb seven days after infection, suggesting no defect or enhancement of