Innate immunity and inflammation in tuberculosis: insights from the zebrafish and therapeutic opportunities

Tuberculosis remains a major problem in much of the world, sickening ~ 10 million people and killing ~1.4 million per year. This is because the only vaccine is not that effective and six months of multidrug treatment are required for cure, making treatment adherence difficult, especially in poor parts of the world which suffer the most from TB. We think that improved therapies and effective preventions require better understanding of how the TB bacteria cause disease and which host responses to infection are beneficial versus harmful. We have developed the zebrafish as a model for TB, exploiting its optical transparency that allows us to visualize how TB bacteria and host cells interact at each step to cause disease. The zebrafish is amenable to genetic mutation, so we can observe the impact of mutations and determine how they alter infection outcome. Our work is leading to completely new TB treatments.