TY - JOUR T1 - Antimycobacterial signaling pathways are differentially regulated in alveolar macrophages of tuberculosis patients JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA2471 VL - 58 IS - suppl 65 SP - PA2471 AU - Elena Ufimtseva AU - Natalya Eremeeva AU - Diana Vakhrusheva AU - Sergey Skornyakov Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA2471.abstract N2 - Tuberculosis (TB), which is caused by the pathogen Mycobacterium tuberculosis (Mtb), remains to be the leading bacterial infectious cause of morbidity and mortality worldwide. In human lungs, the Mtb-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 Mtb.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 Mtb loads in them, examined in the ex vivo 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 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.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2471.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -