Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary infection in rabbits. Oryctolagus cuniculus

In our rabbit model of pulmonary tuberculosis, infection with Mtb HN878, a hyper-virulent W-Beijing strain, results in progressive cavitary disease. However, infection of rabbit lungs with Mtb CDC1551, a hyper-immunogenic strain is effectively controlled overtime, establishing latent Mtb infection. Using these two Mtb strains, we tested the hypothesis that the initial host response in the lungs within hours of infection determines later outcome. The microarray experiments was performed to identify gene expression changes in the Mtb-HN878 or CDC1551- infected rabbit lungs at 3 hours post infection, compared to uninfected naïve rabbit lungs. Overall design: New Zealand White rabbits were infected with Mtb HN878 or CDC1551 at ~3.5log10. At 3 hours post infection, lung tissue from Mtb-infected and uninfected rabbits were isolated and used for total RNA extraction. Total rabbit lung RNA was used for microarray analysis to determine infection induced changes in host gene expression.