Protective immunity against tuberculosis: what does it look like and how do we find it?

Progress towards the development of an effective vaccine against tuberculosis is hampered by the lack of correlative readouts of immune protection, coupled with our limited understanding of the immune mechanisms that determine disease progression versus containment. In this article we discuss the value of microbial readouts of bacterial fitness to probe the host immune environments and determine those host cell subsets that promote or control bacterial growth. Ultimately, we feel that these bacterial reporters will prove to be key in understanding the immune mechanisms underpinning disease outcome, and that this knowledge is critical to any program developing vaccines or immune-modulatory therapeutics as a means of controlling tuberculosis.