th stimuli. These data suggest that JNK1 may play a role in macrophage function in host defense. E. coli has been previously shown to activate JNK1 in macrophages. Furthermore, MCP-1 2/2 mice fail to recruit neutrophils during E. coli pneumonia and have increase bacterial burden in the lung. The link between IL-17A and E. coli pneumonia is supported by the findings that LPS activates IL-17A production in the lung and IL-17A 2/2 mice have increased E. coli burden in urinary tract infection. In addition, RIP2 2/2 mice have increased bacterial burden and decreased IL-17A production in the lung. These data suggest that JNK1 may act downstream of IL17A during E. coli pneumonia. The lack of an impact of JNK1 on host defense against gram-positive bacteria has not been previously reported. Peptidoglycan from S. aureus was shown to require JNK1 to drive IL-8 production in lung type II cells, suggesting a role for JNK1. Our data show a defect in macrophage recruitment but little impact on cytokine production. Recent studies concerning JNK1 and Influenza A infection have focused on the ability of virus to inhibit JNK1 and thus alter host cell apoptosis. JNK1 was shown to be inhibited via viral NS1 protein or host PI3K/AKT activity thus blocking apoptosis of infected cells. These data would suggest that in the absence of JNK1, viral burden may be increased due to a lack of apoptosis, however we observed decreased viral burden in JNK1 2/2 mice. MLK3 2/2 mice, a kinase upstream of JNK1, display increased Influenza A burden due to increased epithelial cell survival and viral replication. The reason for the discrepancy with these data and our findings is unclear. Several studies have reported JNK1 activation following Influenza A infection. In these studies Influenza A drove activation of JNK1, downstream AP-1 transcriptional activity, and cytokine production. Our data show that JNK1 deletion results in an altered inflammatory cellular phenotype in the lung and suppression of KC and IL-10 production. A recent microarray study with a JNK1 inhibitor showed decreased Influenza A induced IL-6 production, although in JNK1 2/2 mice we did not observe this . Our data show JNK1 and Host Defense that JNK1 2/2 mice had increased numbers of lymphocytes in the BAL, but no change in the relative proportion of T cells versus WT mice. JNK1 has been shown to be required for CD8 T cell proliferative responses to IL-2, via regulation of IL-2 receptor, CD25. A separate study showed that CD8 T cell apoptosis requires JNK1 . These findings suggest opposing mecha- nisms by which JNK1 deletion would be expected to either increase or decrease CD8 T cells in TG-02 web response to Influenza A. Our findings indicate a minimal effect on CD8 T cell populations in the lung. At this time it remains to be determined why JNK1 2/2 mice have lower viral burden, but worsened morbidity during Influenza A infection. 7 JNK1 and Host Defense Interactions between the IL-17A and JNK1 signaling pathways have been recently described. In a number of diverse cell types, including airway smooth muscle cells and fibroblasts, IL-17A was shown to stimulate phosphorylation of JNK1 and promote cytokine production. In these studies, pharmacologic inhibition showed that JNK1 is required for the IL-17A induced production of 
inflammatory mediators such as, IL-6, IL-8, eotaxin1, and b-defensin 2. These data suggest that JNK1 is an important downstream signaling kinase in IL-17A induced inflammatory responses. Converse
