Antimycobacterial signaling pathways are differentially regulated in alveolar macrophages of tuberculosis patients

Tuberculosis (TB), which is caused by the pathogen <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), remains to be the leading bacterial infectious cause of morbidity and mortality worldwide. In human lungs, the <i>Mtb</i>-associated molecules interact with the pattern recognition receptors (PRRs) on alveolar macrophages and initiate intracellular signaling cascades, leading to the activation of the nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways to initiate immune reaction against <i>Mtb</i>. The expression of PRRs CD11b and TLR-2, transcription factors HIF-1α, HIF-2α, NF-κB p50 and p65, enzymes iNOS and COX-2, and lipid production were detected for tuberculomas and the lung tissues distant from tuberculomas, with individual <i>Mtb</i> loads in them, examined in the <i>ex vivo</i> cell cultures and on the histological sections obtained from the resected lungs of patients with pulmonary TB. The bacterial control was associated with the pro-inflammatory activation of cells and varying degrees of fibrosis in the discrete lung lesions. The levels of HIF-1α and HIF-2α expression in alveolar macrophages varied across the lung lesions and the TB patients studied, with the HIF-1α isoform appearing to predominate in the cells of the distant lung tissues with focal fibrosis. The enhanced expression of the NF-κB subunits was found in the activated alveolar macrophages mostly in the distant lung tissues characterized by focal and minimal fibrosis, where the cells demonstrated an increased microbicidal potential and low&nbsp;Mtb loads. This analysis is necessary to revise post-operative treatment of TB patients directed to create an effective immunity against Mtb and limit lung damage.