Mycobacterium tuberculosis Load in Host Cells and the Antibacterial Activity of Alveolar Macrophages Are Linked and Differentially Regulated in Various Lung Lesions of Patients with Pulmonary Tuberculosis

• Published in: International journal of molecular sciences 2021-03, Vol.22 (7), p.3452
• Main Authors: Ufimtseva, Elena G, Eremeeva, Natalya I, Umpeleva, Tatiana V, Vakhrusheva, Diana V, Skornyakov, Sergey N
• Format: Article
• Language: English
• Subjects: alveolar macrophages; Alveoli; Antibacterial activity; Bacteria; Biosynthesis; CD11b antigen; CD14 antigen; Cell culture; Chemotherapy; Cyclooxygenase-2; Fibrosis; Granulomas; Host-pathogen interactions; Hypoxia; Hypoxia-inducible factor 1a; immune response; Infections; inflammation; Lesions; Lipids; lung tuberculous lesions; Lungs; Macrophages; Microenvironments; Mycobacterium tuberculosis; Neutrophils; NF-κB protein; Nitric-oxide synthase; Pathogens; Patients; patients with pulmonary tuberculosis; Pattern recognition; Reactive oxygen species; Surgery; TLR2 protein; Toll-like receptors; Transcription factors; Tuberculoma; Tuberculosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22073452

Tuberculosis (TB) is a disease caused by ( ) infection with the formation of a broad range of abnormal lung lesions within a single patient. Although host-pathogen interactions determine disease outcome, they are poorly understood within individual lesions at different stages of maturation. We compared load in a tuberculoma wall and the lung tissue distant from tuberculomas in TB patients. These data were combined with an analysis of activation and bactericidal statuses of alveolar macrophages and other cell subtypes examined both in ex vivo culture and on the histological sections obtained from the same lung lesions. The expression of pattern recognition receptors CD14, CD11b, and TLR-2, transcription factors HIF-1α, HIF-2α, and NF- B p50 and p65, enzymes iNOS and COX-2, reactive oxygen species (ROS) biosynthesis, and lipid production were detected for various lung lesions, with individual loads in them. The walls of tuberculomas with insufficient inflammation and excessive fibrosis were identified as being the main niche for survival (single or as colonies) in non-foamy alveolar macrophages among various lung lesions examined. The identification of factors engaged in the control of infection and tissue pathology in local lung microenvironments, where host-pathogen relationships take place, is critical for the development of new therapeutic strategies.