Background: In 90% of all cases, Mycobacterium tuberculosis infection results in latency rather than active disease, with the pathogen being contained within granulomatous lesions at the site of primary infection. Failure of this containment leads to reactivation of postprimary tuberculosis (TB). The regional immune processes that sustain the delicate balance with persistent M. tuberculosis, however, remain unclear.
Methods: We compared activation statuses, biological functions, and interactions of host immune cells in human nonprogressive tuberculoma and active cavitary tuberculous lung tissue.
Results: Dissection of early granuloma formations revealed differential cellular distribution and activation statuses of distinct cell types in different regions relative to the central caseotic caverna or the tuberculoma in tuberculous lung tissue. In patients with tuberculoma with latent infection, distant parts of lung tissue exhibited strong vascularization and profound proliferative activity, indicating that continuous immune defense is required for mycobacterial containment, which is absent in cavitary tuberculous lung lesions.
Conclusions: We conclude that differential regulation of the local immune response is crucial for the containment of M. tuberculosis and that a continuous antigen-specific cross talk between the host immune system and M. tuberculosis is ensured during latency. This activation requires sufficient supply of nutrients and well-coordinated structural organization, both of which are lost during reactivation of TB.