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.
Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (Mtb) 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 Mtb 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-κB p50 and p65, enzymes iNOS and COX-2, reactive oxygen species (ROS) biosynthesis, and lipid production were detected for various lung lesions, with individual Mtb loads in them. The walls of tuberculomas with insufficient inflammation and excessive fibrosis were identified as being the main niche for Mtb survival (single or as colonies) in non-foamy alveolar macrophages among various lung lesions examined. The identification of factors engaged in the control of Mtb infection and tissue pathology in local lung microenvironments, where host-pathogen relationships take place, is critical for the development of new therapeutic strategies.
['Ufimtseva|Elena G|EG|', 'Eremeeva|Natalya I|NI|', 'Umpeleva|Tatiana V|TV|', 'Vakhrusheva|Diana V|DV|0000-0001-6085-6466', 'Skornyakov|Sergey N|SN|']
D000328:Adult D000900:Anti-Bacterial Agents D058491:Bacterial Load D049109:Cell Proliferation D003584:Cytological Techniques D003955:Diagnostic Tests, Routine D005355:Fibrosis D020869:Gene Expression Profiling D005786:Gene Expression Regulation D054884:Host-Pathogen Interactions D006801:Humans D007107:Immune System D007249:Inflammation D008168:Lung D016676:Macrophages, Alveolar D009169:Mycobacterium tuberculosis D017382:Reactive Oxygen Species D014376:Tuberculosis D014397:Tuberculosis, Pulmonary D055815:Young Adult
Mycobacterium tuberculosis alveolar macrophages patients with pulmonary tuberculosis inflammation fibrosis immune response lung tuberculous lesions