New insights on the nature of latent tuberculosis infection and its treatment.

Nowadays, there is no conclusive theory explaining the latent tuberculosis infection (LTBI). LTBI is reviewed herein as a standard progression of M. tuberculosis in the context of the usual microaerobiosis present in the host's tissues and displaying their main virulent factors: slow metabolism; cell wall thickness and ability to induce intragranulomatous necrosis. Therefore, latent bacilli (LB) would be generated by the irruption of specific immunity forcing bacilli to remain in a stationary phase (SP) inside the necrotic tissue. This tissue is crucial because it maintains a stable LB population and prolongs the production of foamy macrophages which facilitate the LB escape to the alveolar spaces. In the alveolar spaces, LB will regrow and, once freed in this privileged space, they will induce new granulomas -less developed because they are better controlled by immunity. This explains the ability of LB to face the chance to be drained as a consequence of the constant cellular turnover, and to survive for a long time in the lung. This activity also supports the hypothesis that generation of active TB highly depends on the probability of the LB regrowth in a favorable zone (i.e., in the pulmonary apex). This "dynamic" hypothesis faces a more classic one (or "static") essentially based on the presence of a "resuscitation" factor that would reactivate "dormant" bacilli in old lesions in the apex. Current possibilities for LTBI treatment are reviewed according to this "dynamic hypothesis", from the standard chemotherapy to the introduction of therapeutic vaccines and anti-inflammatory treatments.