Effect of Mycobacterium tuberculosis on immunohistochemical parameters of stable pulmonary tuberculoma

For millennia, the mankind has been trying to fight the causative agent of tuberculosis, Mycobacterium tuberculosis, but morbidity and mortality rates, unfortunately, remain high all over the world. The purpose of our work was to specify changes of immunohistochemical parameters in different areas of the lungs in stable tuberculosis. We have studied 30 cases of stable tuberculosis in male patients. The study concerned two 2 areas: the tuberculoma capsule and adjacent areas (perifocal zones). The comparison group consisted of resected material from upper lobes of the right lung, taken from 10 men who died in accidents and did not have tuberculosis during their lifetime. This group was called “conditionally healthy” controls. To assess the signs of local immune response, an immunohistochemical method was used using monoclonal antibodies to CD8, CD4, CD79a, Fascin. When assessing location of the markers expressed in the lung tissues of “conditionally healthy” group, the number of CD4⁺ and CD8⁺ cells was determined mainly in the interstitial space. The numbers of CD4⁺ cells in this study group prevailed over CD8⁺ cells, whereas CD79a⁺ and Fascin⁺ cells were found in small quantities within interstitial space. In stable tuberculoma, a greater number of lymphocytes were detected in the capsule with a predominance of T killers over T helpers. In perifocal area of stable tuberculoma, the number of immune cells was reduced when compared to the “conditionally healthy” group. At the same time, we determined the areas where CD4-positive lymphocytes formed contacts with interstitial macrophages. The number of CD79a positive cells was mainly determined in the connective tissue capsule of tuberculoma, with single cells on the periphery, being close to macrophages. Fascin-positive cells in both capsule and perifocal zone of stable tuberculoma were rare, being mainly localized around blood vessels. When studying correlations in the “conditionally healthy” group, a moderate positive relationship between cytotoxic lymphocytes and T helper cells was revealed. In the capsular area of stable tuberculoma, strong positive correlations were found for CD4⁺/CD79a and CD79a/CD8⁺ pairs; in the peripheral zone of the lungs, correlations were revealed only between CD79a and CD8⁺ cells. Hence, the degree of activity of the tuberculosis process in the capsule and perifocal areas of stable pulmonary tuberculosis is associated with different cellular interactions which exert double control from both cellular and humoral immunity.

1. Gimaldinova N.E., Lyubovtseva L.A. Histamine-containing lung cell structures in certain forms of secondary tuberculosis. Zhurnal anatomii i gistopatologii = Journal of Anatomy and Histopathology, 2022, Vol. 11, no. 1, pp. 28-35. (In Russ.)

2. Gimaldinova N.E., Lyubovtseva L.A., Lyubovtseva E.V. Neurotransmitter level in neuroamincontaining lung structures in different forms of tuberculosis. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2021, Vol. 11, no. 6, pp. 1067-1074. (In Russ.) doi: 10.15789/2220-7619-ДОП-1632.

3. Elipashev A.A., Nikolsky V.O., Shprykov A.S. Dependence of the activity of tuberculous inflammation (according to morphological data) on the different duration of the disease in patients with limited drug-resistant pulmonary tuberculosis. Vestnik novykh meditsinskikh tekhnologiy. Elektronnoe izdanie = Bulletin of New Medical Technologies. Electronic Edition, 2016, no. 1. рр. 54-59. Available at: http://www.medtsu.tula.ru/VNMT/Bulletin/E2016-1/2-1.pdf. (In Russ.)

4. Kravtsov A.L., Kozhevnikov V.A., Klyueva S.N., Kudryavtseva O.M., Schukovskaya T.N., Mikshis N.I., Bugorkova S.A. Cellular immune status indicators of anti-plague vaccinated persons, living on the caspian sandy natural plague focus territory. Epidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccinal Prevention, 2019, Vol. 18, no. 4, pp. 67-74. (In Russ.)

5. Nechaeva O.B. Socially important infectious diseases posing a biological threat to the population of Russia. Tuberkulez i bolezni legkikh = Tuberculosis and Lung Diseases, 2019, Vol. 97, no. 11, pp. 7-17. (In Russ.)

6. Fentisov V.V. Comparative study of the incidence of tuberculosis in the adult population by age and gender. Sovremennye problemy nauki i obrazovaniya = Modern Problems of Science and Education, 2022, no. 3. [Electronic resource]. Available at: https://science-education.ru/ru/article/view?id=31775. (In Russ.)

7. Khozhimatov H.O. Tuberculosis as a global medical and social problem (a brief literary review). Aktualnye problemy gumanitarnykh i estestvennykh nauk = Actual Problems of Humanities and Natural Sciences, 2014, no. 5-2, pp. 211-213. (In Russ.)

8. Kholodok O.A., Grigorenko A.A., Cheremkin M.I. Pulmonary tuberculosis as a form of tuberculosis process. Byulleten fiziologii i patologii dykhaniya = Bulletin of Physiology and Pathology of Respiration, 2014, no. 53, pp. 126-131. (In Russ.)

9. Shaimardanova A.F. Possibilities of differential X-ray diagnostics of tuberculosis and peripheral lung cancer. Byulleten meditsinskikh internet-konferentsiy = Bulletin of Medical Internet Conferences, 2013, Vol. 3, Iss. 2, p. 200. (In Russ.)

10. Anes E., Pires D., Mandal M., Azevedo-Pereira J.M. ESAT-6 a major virulence factor of Mycobacterium tuberculosis. Biomolecules, 2023, Vol. 13, 968. doi: 10.3390/biom13060968.

11. Bhattarai N., Malhotra S., Crane G.M. CD79a. Stains & CD markers CD79a. Available at: https://www.pathologyoutlines.com/topic/cdmarkerscd79a.html. (Accessed April 21, 2024).

12. Ernst W.A., Thoma-Uszynski S., Teitelbaum R., Ko C., Hanson D.A., Clayberger C., Krensky A.M., Leippe M., Bloom B.R., Ganz T., Modlin R.L. Granulysin, a T cell product, kills bacteria by altering membrane permeability. J. Immunol., 2000, Vol. 165, Iss. 12, pp. 7102-7108.

13. Kozakiewicz L., Phuah J., Flynn J., Chan J. The role of B cells and humoral immunity in Mycobacterium tuberculosis infection. Adv. Exp. Med. Biol., 2013, Vol. 783, pp. 225-250.

14. Rahlwes K.C., Dias B.R.S., Campos P.C., Alvarez-Arguedas S., Shiloh M.U. Pathogenicity and virulence of Mycobacterium tuberculosis. Virulence, 2023, Vol. 14, Iss. 1, 2150449. doi: 10.1080/21505594.2022.2150449.

15. Sia J.K., Bizzell E., Madan-Lala R., Rengarajan J. Engaging the CD40-CD40L pathway augments T-helper cell responses and improves control of Mycobacterium tuberculosis infection. PLoS Pathog., 2017, Vol. 13, e1006530. doi: 10.1371/journal.ppat.1006530.

16. Stenger S., Hanson D.A., Teitelbaum R., Dewan P., Niazi K.R., Froelich C.J., Ganz T., Thoma-Uszynski S., Melian A., Bogdan C., Porcelli S.A., Bloom B.R., Krensky A.M., Modlin R.L. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science, 1998, Vol. 282, Iss. 5386, pp. 121-125.

17. Zhang N., Gao Y., Bian Q., Wang Q., Shi Y., Zhao Z., Yu H. The role of fascin-1 in the pathogenesis, diagnosis and management of respiratory related cancers. Front. Oncol., 2022, Vol. 12, 948110. doi: 10.3389/fonc.2022.948110.