Understanding latent tuberculosis: a moving target

Abstract

Tuberculosis (TB) remains a threat to the health of people worldwide. Infection with Mycobacterium tuberculosis can result in active TB or, more commonly, latent infection. Latently infected persons, of which there are estimated to be approximately 2 billion in the world, represent an enormous reservoir of potential reactivation TB, which can spread to other people. The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease.

FIGURE 1

The spectrum of M. tuberculosis infection outcome is depicted. The clinical outcomes of active (red line) and latent (blue line) infection are subdivided to reflect the variability of infection in those categories. Bacterial burden, shown by the dashed orange line, is expected to increase up the spectrum of infection. The seesaws reflect the balance of pro- (P) and anti-inflammatory (A) factors in the granuloma. At the lower end of the latency spectrum, these two factors are well balanced, controlling bacterial growth with minimal pathology. As one advances up the spectrum, the balance can shift with either too much proinflammatory or too much anti-inflammatory activity, which can lead to poor control of bacteria and increased pathology. The purple line reflects the risk of reactivation in the latent spectrum.