Of the 32 genes in the fMLP stimulated network, 24 and 13 genes were upregulated at 3 hours in the HN878 and CDC1551 infected animals, respectively. A higher number of genes were significantly downregulated in necessary CDC1551, than in HN878 infected lungs. In this network, most of the genes that encode cytokines, chemokines, enzymes and receptors were upregulated only in the HN878 infected animals. Six genes, ITGB1, PTEN, HGF, ICAM2, FN1 and S100A9, were more upregulated in the CDC1551 infected rabbit lungs. Among the SDEG observed at 3 hours following Mtb infection, a subset of 40 genes are involved in the recruit ment and activation Inhibitors,Modulators,Libraries of PMN. Of these, 29 were upregulated and 10 were downregulated in the HN878 infected rabbit lungs.
The majority of upregulated genes encode cytokines and chemokines, including CCL4, CXCL10, CCL5, TNF and IL15, as well as cell surface re ceptors, Inhibitors,Modulators,Libraries such as FCGR2A, FPR1, FPR2 and TLR4, enzymes and the transcriptional regulator, STAT1. In contrast, CDC1551 infection was associated with upregulation Inhibitors,Modulators,Libraries of only 12 genes and downregulation of 26 genes in this path way. Taken together, both the number of Inhibitors,Modulators,Libraries upregulated genes and the magnitude of their expression in the selected networks were generally higher in the lungs of HN878 infected animals. However, in the CDC1551 infected rabbits, upregulation of a subset of the genes belonging to these networks was noted.
Interaction between inflammatory response, STAT1, macrophage and PMN activation networks To identify key genes involved in the cellular processes driving the course of infection after implantation of HN878 or CDC1551 in rabbit lungs, we examined the number of genes shared among the host Inhibitors,Modulators,Libraries inflammatory response, STAT1 activation, PMN recruitment and acti vation, and macrophage activation networks. Of the 281 SDEG involved in the host inflammatory response, 150 were also shared by the STAT1 regulation network. Moreover, all the genes in volved in the PMN recruitment and activation and macrophage activation networks were part of the host inflammatory response network and many were also part of the STAT1 network. In addition, there were 17 genes commonly regulated by all four biological processes. The 4 week host response to infection with Mtb HN878 and CDC1551 To validate our hypothesis that the outcome following Mtb infection is determined by the very early changes in the host immune response, we analyzed the bacillary load, histology and the previously selected net work gene expression profiles in the lungs of HN878 or CDC1551 infected rabbits at 4 weeks. As shown in Figure 6A, rabbit lungs infected with similar numbers of HN878 and CDC1551 at 3 hours, multiplied similarly during the first 2 weeks, reaching 5. 7 0. 7 and 5. 4 0. 8 log10 http://www.selleckchem.com/products/tofacitinib-cp-690550.html CFU, respectively.