Histological examination of the lungs at 4 weeks showed striking dif ferences in pathology between HN878 and CDC1551 infected rabbits. Higher numbers of larger cellular granulomas were observed in the HN878 infected rabbit lungs compared to the CDC1551 infected animals. In addition, the cellular composition and distri bution in the granulomas was different in the HN878 sellckchem infected rabbits, macrophages and lymphocytes were intermixed while in CDC1551 infected rabbits the granu lomas were much more differentiated with a central area of macrophages and well demarcated lymphocytic cuffs. We next analyzed the expression of the same network genes examined at 3 hours post infection using a genome wide transcriptome of rabbit lungs infected for 4 weeks.

The selected networks Inhibitors,Modulators,Libraries included the host inflammatory response, STAT1 regulation, PMN activation, fMLP stimu lation and macrophage Inhibitors,Modulators,Libraries activation. Of the 284 SDEG in the in flammatory network at 3 hours, a subset of 164 and 67 genes were also differ entially expressed at 4 weeks in the lungs of HN878 or CDC1551 infected rabbits, respectively. Moreover, 120 and 217 genes previously dif ferentially expressed, were not significantly expressed at this time in HN878 or CDC1551 infected rabbit lungs, respectively. Thus, although the inflammatory response was generally dampened in both groups by 4 weeks of infection, similar to the observations at 3 hours, a much higher number of SDEG were upregulated in the HN878 infected animals, while the majority of these SDEG were not significantly expressed in the CDC1551 infected rabbits.

At 3 hours, we observed an upregulation of 42 of the 43 SDEG involved in the STAT1 interaction network in the lungs of HN878, Inhibitors,Modulators,Libraries compared to only 23 in CDC1551 infected rabbit lungs. Consistent with our findings at 3 hours, 32 of the 43 SDEG involved in the STAT1 interaction network Inhibitors,Modulators,Libraries were upregulated in the HN878, compared to only 4 SDEG in the CDC1551 infected rabbit lungs. Thus, similar to the inflammatory response network, the STAT1 interaction network shows a conservation of the gene expression pattern between 3 hours and 4 weeks. Relative to 3 hours, over 50% of the SDEG in each Inhibitors,Modulators,Libraries of the networks involved in the activation of macrophage, PMN and fMLP stimu lation were differentially expressed at 4 weeks, with the majority upregulated only in the lungs of HN878 infected rabbits. In contrast, only about 20% of SDEG in each of these networks were expressed in the CDC1551 infected rabbit lungs with the majority down regulated. Taken together, compared to 3 hours, the gene expression pattern shows a general dampening in the activation of PMN, macrophage and, fMLP stimula tion networks at 4 add to your list weeks in both HN878 and CDC1551 infected rabbit lungs.