Significance of the Notch Signaling Pathway in Modulating the Differentiation of Main T-Lymphocytes Populations in Patients with Infiltrative Pulmonary Tuberculosis
https://doi.org/10.58838/2075-1230-2023-101-4-34-39
Abstract
The objective: to evaluate the modulating effect of the Notch signaling pathway on differentiation of Th1 and Th2 lymphocytes in vitro in patients with infiltrative pulmonary tuberculosis.
Subjects and Methods. 14 new patients with infiltrative pulmonary tuberculosis were enrolled in the study. Mononuclear leukocytes were isolated from blood by gradient centrifugation. Only Mycobacterium tuberculosis antigens in the form of the CFP10-ESAT6 protein or together with Y-secretase inhibitor DAPT (5 μМ/l or 10 μМ/l) were added to the incubation medium. Cells were cultured for 72 h in a complete nutrient medium with 5% CO2 at 37°C. Counts of Th1 and Th2 lymphocytes were determined by flow cytometry by evaluating the expression of CD4 receptor and intracellular transcription factors T-bet and GATA-3.
Results. Cell stimulation with the CFP10-ESAT6 protein was accompanied by increasing number of Th1 and Th2 lymphocytes only in patients with pulmonary tuberculosis resistant to isoniazid + rifampicin. Adding DAPT at the concentration of 10 μМ/L to the incubation medium in these patients led to the growing number of Th1 lymphocytes and decrease in Th2 lymphocytes. In pulmonary tuberculosis patients who were susceptible to isoniazid + rifampicin, only decrease in the number of Th2-lymphocytes was regeistered. In all groups of subjects, suppression of the Notch signaling pathway led increase in the Th1/Th2 index versus Th1/Th2 stimulated with CFP10-ESAT6 antigens.
About the Authors
A. E. Sanina
Siberian State Medical University, Russian Ministry of Health
Russian Federation
Russian Federation
Anna E. Sanina - Post Graduate Student of Pathophysiology Department.
39, Uchebnaya St., Tomsk, 634034
Phone: +7 (999) 177-43-03
V. A. Serebryakova
Siberian State Medical University, Russian Ministry of Health
Russian Federation
Russian Federation
Valentina A. Serebryakova - Doctor of Medical Sciences, Associate Professor, Professor of Pharmacology Department.
39, Uchebnaya St., Tomsk, 634034
Phone: +7 (913) 118-18-78
O. I. Urazova
Siberian State Medical University, Russian Ministry of Health
Russian Federation
Russian Federation
Olga I. Urazova - Doctor of Medical Sciences, Professor, Correspondent Member of RAS, Head of Pathophysiology Department, Professor of Department of Integrated Information Security of Electronic Computing System, Tomsk State University of Control Systems and Radioelectronics.
39, Uchebnaya St., Tomsk, 634034
Phone: +7 (903) 913-14-83
A. A. Gadzhiev
Siberian State Medical University, Russian Ministry of Health
Russian Federation
Russian Federation
Alibey A. Gadzhiev - Student of General Medicine Department.
39, Uchebnaya St., Tomsk, 634034
Phone: +7 (923) 441-55-12
E. P. Stepanova
Tomsk Phthisiopulmonology Medical Center, Russian Ministry of Health
Russian Federation
Russian Federation
Ekaterina P. Stepanova - Head of Respiratory Tuberculosis Department.
17, Rozy Luxemburg St., Tomsk, 634009
Phone: +7 (906) 950-70-84
T. E. Kononova
Siberian State Medical University, Russian Ministry of Health
Russian Federation
Russian Federation
Tatyana E. Kononova - Candidate of Medical Sciences, Associate Professor of Pathophysiology Department.
39, Uchebnaya St., Tomsk, 634034
Phone: +7 (923) 403-80-05
References
1. Churina E. G., Popova A. V., Urazova O. I., Patysheva M. R., Kolobovnikova Yu. V., Chumakova S. P. Expression of scavenger receptors CD163, CD204, and CD206 on macrophages in patients with pulmonary tuberculosis. Bulleten Sibirskoy Meditsiny, 2022, vol. 21, no. 4, pp. 140-149. (In Russ.) https://doi.org/10.20538/1682-0363-2022-4-140-149
2. Abebe F. Synergy between Th1 and Th2 responses during Mycobacterium tuberculosis infection: A review of current understanding. Int. Rev. Immunol., 2019, vol. 38, no. 4, pp. 172-179. https://doi.org/10.1080/08830185.2019.1632842
3. Burt P., Peine M., Peine C., Borek Z., Serve S., FloBdorf M., Hegazy A. N., Hofer T., Lohning M., Thurley K. Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells. Front. Immunol., 2022, no. 13, pp. 928018. https://doi.org/10.3389/fimmu.2022.928018
4. Dua B., Upadhyay R., Natrajan M., Arora M., Kithiganahalli Narayanaswamy B., Joshi B. Notch signaling induces lymphoproliferation, T helper cell activation and Th1/Th2 differentiation in leprosy. Immunol. Lett., 2019, no. 207, pp. 6-16. https://doi.org/10.1016/j.imlet.2019.01.003
5. Kapoor A., Nation D. A. Role of Notch signaling in neurovascular aging and Alzheimer's disease. Semin. Cell Dev. Biol., 2021, no. 116, pp. 90-97. https://doi.org/10.1016/j.semcdb.2020.12.011
6. Kathamuthu G. R., Sridhar R., Baskaran D., Babu S. Dominant expansion of CD4+, CD8+ T and NK cells expressing Th1/Tc1/Type 1 cytokines in culture-positive lymph node tuberculosis. PLoS One, 2022, vol. 17, no. 5, pp. e0269109. https://doi.org/10.1371/journal.pone.0269109
7. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern. Med. Rev., 2003, vol. no. 3, pp. 223-46.
8. Kononova T. E., Urazova O. I., Novitskii V. V., Esimova I. E., Churina E. G. Subpopulation structure of IFNY-producing T lymphocytes in patients with pulmonary tuberculosis. Bull. Exp. Biol. Med., 2018, vol. 165, no. 3, pp. 311-314. https://doi.org/10.1007/s10517-018-4157-z
9. Li G., Yang F., He X., Liu Z., Pi J., Zhu Y., Ke X., Liu S., Ou M., Guo H., Zhang Z., Zeng G., Zhang G. Anti-tuberculosis (TB) chemotherapy dynamically rescues Th1 and CD8+ T effector levels in Han Chinese pulmonary TB patients. Microbes Infect., 2020, vol. 22, no. 3, pp. 119-126. https://doi.org/10.1016/j.micinf.2019.10.001
10. Lim J. S., Ibaseta A., Fischer M. M., Cancilla B., O'Young G., Cristea S., Luca V. C., Yang D., Jahchan N. S., Hamard C., Antoine M., Wislez M., Kong C., Cain J., Liu Y. W., Kapoun A. M., Garcia K. C., Hoey T., Murriel C. L., Sage J. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature, 2017, vol. 545, no. 7654, pp. 360-364. https://doi.org/10.1038/nature22323
11. Maglione P. J., Chan J. How B cells shape the immune response against Mycobacterium tuberculosis. Eur. J. Immunol., 2009, vol. 39, no. 3, pp. 676-86. https://doi.org/10.1002/eji.200839148
12. Mayer-Barber K. D., Barber D. L. Innate and Adaptive Cellular Immune Responses to Mycobacterium tuberculosis Infection. Cold Spring Harb. Perspect. Med., 2015, vol. 5, no, 12, pp. a018424. https://doi.org/10.1101/cshperspect.a018424
13. Neal L. M., Qiu Y., Chung J., Xing E., Cho W., Malachowski A. N., Sandy-Sloat A. R., Osterholzer J. J., Maillard I., Olszewski M. A. T Cell-Restricted Notch Signaling Contributes to Pulmonary Th1 and Th2 Immunity during Cryptococcus neoformans Infection. J. Immunol., 2017, vol. 199, no. 2 pp. 643-655. https://doi.org/10.4049/jimmunol.1601715
14. Perna A., Marathe S., Dreos R., Falquet L., Akarsu Egger H., Auber L. A. Revealing NOTCH-dependencies in synaptic targets associated with Alzheimer's disease. Mol. Cell Neurosci., 2021, no. 115, pp. 103657. https://doi.org/10.1016/j.mcn.2021.103657
15. Ravesloot-Chavez M. M., Van Dis E., Stanley S. A. The Innate Immune Response to Mycobacterium tuberculosis Infection. Annu. Rev. Immunol., 2021, no. 39, pp. 611-637. https://doi.org/10.1146/annurev-immunol-093019-010426
16. Santos J. H. A., Buhrer-Sekula S., Melo G. C., Cordeiro-Santos M., Pimentel J. P. D., Gomes-Silva A., Costa A. G., Saraceni V., Da-Cruz A. M., Lacerda M. V. G. Ascaris lumbricoides coinfection reduces tissue damage by decreasing IL-6 levels without altering clinical evolution of pulmonary tuberculosis or Th1/Th2/Th17 cytokine profile. Rev. Soc. Bras. Med. Trop., 2019, no. 52, pp. e20190315. https://doi.org/10.1590/0037-8682-0315-2019
17. Sha S., Shi X., Deng G., Chen L., Xin Y., Ma Y. Mycobacterium tuberculosis Rv1987 induces Th2 immune responses and enhances Mycobacterium smegmatis survival in mice. Microbiol. Res., 2017, no. 197, pp. 74-80. https://doi.org/10.1016/j.micres.2017.01.004
18. Sharif A., Shaji A., Chammaa M., Pawlik E., Fernandez-Valdivia R. Notch Transduction in Non-Small Cell Lung Cancer. Int. J. Mol. Sci., 2020, vol. 21, no. 16, pp. 5691. https://doi.org/10.3390/ijms21165691
19. Siebel C., Lendahl U. Notch Signaling in Development, Tissue Homeostasis, and Disease. Physiol Rev., 2017, vol. 97, no. 4, pp. 1235-1294. https://doi.org/10.1152/physrev.00005.2017
20. Urazova O. I., Churina E. G., Hasanova R. R., Novitskiy V. V., Poletika V. S. Association between polymorphisms of cytokine genes and secretion of IL-12P70, IL-18, and IL-27 by dendritic cells in patients with pulmonary tuberculosis. Tuberculosis, 2019, vol. 115, pp. 56-62. https://doi.org/10.1016/j.tube.2019.02.003
21. Verma N. K., Fazil M. H., Ong S. T., Chalasani M. L., Low J. H., Kottaiswamy A. P. P., Kizhakeyil A., Kumar S., Panda A. K., Freeley M., Smith S. M., Boehm B. O., Kelleher D. LFA-1/ICAM-1 ligation in human T cells promotes Th1 polarization through a GSK3e signaling-dependent Notch pathway. J. Immunol., 2016, vol. 197, no. 1, pp. 108-118. https://doi.org/10.4049/jimmunol.1501264
22. Vijayaraghavan J., Osborne B. A. Notch and T Cell Function - A Complex Tale. Adv. Exp. Med. Biol., 2018, no. 1066, pp. 339-354. https://doi.org/10.1007/978-3-319-89512-3_17
Review
For citations:
Sanina A.E., Serebryakova V.A., Urazova O.I., Gadzhiev A.A., Stepanova E.P., Kononova T.E. Significance of the Notch Signaling Pathway in Modulating the Differentiation of Main T-Lymphocytes Populations in Patients with Infiltrative Pulmonary Tuberculosis. Tuberculosis and Lung Diseases. 2023;101(4):34-39. (In Russ.) https://doi.org/10.58838/2075-1230-2023-101-4-34-39
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