The goal of this project is to design a novel model to study the roles of tumor necrosis factor-alpha (TNF-a) during Mycobacterium tuberculosis (M. tb) growth and persistent and latent infection. It has been known for many years that M. tuberculosis has the ability to persist in healthy individual and that it can be reactivated when the immune system is weaken. Reactivation is an exciting field of research but one that is limited in experimental model. One of the best models to study M. tuberculosis latency and reactivation is the Cornell model. However, there have been only few report cases of using the Cornell model because it is time consuming and variations of the results are often observed depending on the regimens of drug treatments and the means of reactivation. The transgenic mice will be very useful model to study latency in that the time required for reactivation could be shorten. We will use the mice to study the effect of the lost of this cytokine on granuloma formation, other cytokines profiles and lymphocytes recruitment during M. tuberculosis infection. We will exploit the signature tagged mutagenesis screen to search for mutants that fail to be reactivated. If we succeed in isolating reactivation mutants, many exciting areas of research would soon follow. ? ?
