Different antimycobacterial activity of macrophages in various lung tuberculosis legions of patients

Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a highly infectious and successful human pathogen. In human lungs, Mtb are recognized and engulfed by alveolar macrophages, leading to the release of many antimycobacterial factors, including reactive oxygen species (ROS) and nitric oxide produced by the enzyme inducible nitric oxide synthase (iNOS). However, Mtb can survive, replicate, and persist in human lungs for a long time.

In this study with using immunofluorescence assay, we examined the number of Mtb-infected alveolar macrophages and the quantity of ROS- and iNOS-positive cells in the ex vivo cell cultures obtained from the resected lung tissues with different TB lesions: tuberculomas and lung parts distant from macroscopic TB lesions, - in the same patients with pulmonary MDR-TB as described in (Ufimtseva, E. et al. PLOS ONE 2018; 13:e0191918). We found more alveolar macrophages with single Mtb or Mtb in colonies, including those with cording morphology, in the wall of tuberculomas than in the distant lung tissues of the same TB patients. Conversely, many alveolar macrophages with the antimicrobial agents examined were detected in the distant lung tissues, but not in the wall of tuberculomas. Thus, TB patients’ alveolar macrophages were characterized by different microbicidal potential and contained a different number of Mtb in various TB legions of the same resected lungs.

Finally, our findings provide a crucial insight into Mtb pathogenesis during human TB disease. Studies of the mechanisms of Mtb survival within alveolar macrophages during human TB disease are extremely important for the development of new methods for TB treatment.