We have studied the risk of progression to active pulmonary tuberculosis (TB) among a population of Cambodian rural poor suffering from one of the highest global incidences of TB. Together with a community-based TB program, we have established a research partnership that has demonstrated the association of a particular HLA binding motif and progression to active pulmonary TB. We have also shown that candidate gene polymorphisms are ethnic specific and unique in Cambodia and are likely markers for as yet unidentified disease susceptibility and resistance loci. We have also uncovered a high incidence of antigen-specific anergy to purified protein derivative among patients with active pulmonary TB and have correlated this with an expansion of immunosuppressive IL-10 producing T cells and other impaired T cell responses to mycobacterial antigens. These experiments lend insight into TB susceptibility and the molecular mechanisms of antigen-specific anergy. Moreover, they demonstrate that a partnership between TB cure and scientific discovery is possible in even the most impoverished settings.