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Fragments of the lungs of 84 patients with fibrocavernous tuberculosis (FCT) with verified isolation of mycobacteria (FCT-MBT+) and 79 patients with FCT without bacterial excretion (FCT-MBT–) were studied. Immunoprofiling of lung tissue cell populations with markers of type 1 T-helpers and cytotoxic lymphocytes made it possible to determine a pool of epithelioid cells with a large vesicular nucleus of a rounded-oval shape, demonstrating a positive cytoplasmic reaction for both CD4 and CD8 receptors, exclusively in patients with active bacterial excretion. Localization corresponded to intact lung tissue at the border of the cavity resection and pericavernous areas of emphysema. Groups of such cells were visualized in the lumen of the alveoli or single cells in the «niches» of the epithelial lining. Comparison with routine staining with hematoxylin and eosin, as well as verification with the macrosialin marker CD68, proved the histiocytic origin of this cell population. At the same time, CD68+, CD4+, CD8+showed a negative reaction with VEGF-A, which excluded their belonging to functional type 2 macrophages with remodeling activity in relation to lung tissue. Analysis of IHC reactions with a marker of irreversible induction of apoptosis in the macrophage pool showed that Caspase-3 expression was visualized in all CD68+VEGF-A– macrophages. However, the intensity of the cytoplasmic reaction was most pronounced in the zone of specific granulation tissue of functional type 1 macrophages and in the pericavernous clusters of CD68+, CD4+, CD8+cells. It was shown that IHC identification of a population of macrophages with a cytotoxic immunophenotype (CD68+, CD4+, CD8+) in the lung tissue is a diagnostic and prognostic indicator of PCT activation and dissemination.
1. Desikan P., Rangnekar A. Host-targeted therapy for tuberculosis: Time to revisit the concept. The Indian Journal of Medical Research. 2018;147(3):233-238. https://doi.org/10.4103/ijmr.IJMR_652_17
2. Kaur M., Garg T., Narang R. K. A review of emerging trends in the treatment of tuberculosis. Artificial Cells, Nanomedicine, and Biotechnology. 2016;44(2):478-484. https://doi.org/10.3109/21691401.2014.962745
3. Upadhyay R., Sanchez-Hidalgo A., Wilusz C. J., Lenaerts A. J., Arab J. [et al.]. Host Directed Therapy for Chronic Tuberculosis via Intrapulmonary Delivery of Aerosolized Peptide Inhibitors Targeting the IL-10-STAT3 Pathway. Scientific Reports. 2018;8(1):16610. https://doi.org/10.1038/s41598-018-35023-0
4. Golubinskaya E. P., Filonenko T. G., Kubyshkin A. V. Features of the immunophenotype of the macrophage population in fibrocavernous pulmonary tuberculosis. Bulleten sibirskoj medicini. – Bulletin of Siberian medicine. 2019;18(1):190-201. (In Russ.). https://doi.org/10.20538/1682-0363-2019-1-190-200
5. Deretic V., Klionsky D. J. Autophagy and inflammation: a special review issue. Autophagy. 2018;14:178-180. https://doi.org/10.1080/15548627.2017.1412229
6. Doster R. S., Rogers L. M., Gaddy J. A., Aronoff D. M. Macrophage extracellular traps: a scoping review. Journal of Innate Immunology. 2017;10:3-13. https://doi.org/10.1159/000480373
7. Golubinskaya E. P., Filonenko T. G., Ermola Yu. A. Ultrastructural features of the components of the airborne lung barrier in fibro-cavernous pulmonary tuberculosis. Meditsinskii vestnik Severnogo Kavkaza. – Medical News of North Caucasus. 2019;14(1):180-186. (In Russ.). https://doi.org/10.14300/mnnc.2019.14010
8. Italiani P., Boraschi D. From monocytes to M1/M2 macrophages: phenotypical vs. functional differentiation. Frontiers in Immunology. 2014;5:514. https://doi.org/10.3389/fimmu.2014.00514
9. Tan S. Y. S., Krasnow M. A. Developmental origin of lung macrophage diversity. Development. 2016;143:1318-1327. https://doi.org/10.1242/dev.129122
10. Gleeson L. E., Sheedy F. J., Palsson-McDermott E. M., Triglia D., O’Leary S. M. [et al.]. Cutting edge: Mycobacterium tuberculosis induces aerobic glycolysis in human alveolar macrophages that is required for control of intracellular bacillary replication. Journal of Immunology. 2016;196:2444-2449. https://doi.org/10.1165/rcmb.2018-0162OC
11. Dallenga T., Linnemann L., Paudyal B., Repnik U., Griffiths G., Schaible U. E. Targeting neutrophils for host-directed therapy to treat tuberculosis. International Journal of Medical Microbiology. 2018;308(1):142-147. https://doi.org/10.1016/j.ijmm.2017.10.001
12. Boddaert J., Bielen K., Jongers B., Manocha E., Yperzeele L. [et al.]. CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia. PLoS ONE. 2018;13(1):e0186937. https://doi.org/10.1371/journal.pone.0186937
13. Murray P. J., Allen J. E., Biswas S. K., Fisher E. A., Gilroy D. W., Goerdt S. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14-20. https://doi.org/10.1016/j.immuni.2014.06.008
14. Zloza A., Al-Harthi L. Multiple populations of T lymphocytes are distinguished by the level of CD4 and CD8 coexpression and require individual consideration. Journal of Leukocite Biology. 2006;79:4-6. https://doi.org/10.1189/jlb.0805455
15. Sarrabayrouse G., Bossard C., Chauvin J.-M., Jarry A., Meurette G., Quévrain E. CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease. PloS Biol. 2014;12(4):e1001833. https://doi.org/10.1371/journal.pbio.1001833
Keywords: tuberculosis, ICH, T-lymphocytes, macrophage