Tuberculosis remains one of the most significant infectious disease threats to global health despite the availability of effective antimicrobials for more than 50 years. The focus of this Keystone Symposia meeting is on co-morbidities that are major driving factors in the TB pandemic and that may cause informative perturbations of immunity. This symposium explores metabolic disorders, environmental exposures, co-infections, age and genetic variants that influence host-pathogen interactions in TB. Plenary sessions will combine rather than separate topics focused on the host and the pathogen, and perspectives from laboratory and field studies. Speakers are encouraged to challenge existing dogma and offer new paradigms as a basis for more effective approaches to TB prevention and treatment.