tibljТуберкулез и болезни легкихTuberculosis and Lung Diseases2075-12302542-1506Медицинские знания и технологии10.21292/2075-1230-2021-99-12-57-64tiblj-1600Research ArticleОБЗОРREVIEWДиагностика активности туберкулезной инфекции методами транскрипционного анализаDiagnosis of Tuberculosis Infection Activity by Methods of Transcriptional AnalysisРубаковаЭ. И.RubakovaE. I.

Рубакова Эльвира Ивановна, кандидат биологических наук, старший научный сотрудник лаборатории иммуногенетики.

107564, Москва, Яузская аллея, д. 2.

Тел.: +7 (499) 785-90-72.

Elvira I. Rubakova, Candidate of Biological Sciences, Senior Researcher of Immunogenetics Laboratory.

2, Yauzskaya Alleya, Moscow, 107564.

Phone: +7 (499) 785-90-72.

rubakova@mail.ruКондратьеваТ. К.KondratievaT. K.

Кондратьева Татьяна Константиновна, доктор биологических наук, ведущий научный сотрудник лаборатории иммуногенетики.

107564, Москва, Яузская аллея, д. 2.

Тел.: +7 (499) 785-90-72.

Tatiana K. Kondratieva, Doctor of Biological Sciences, Leading Researcher of Immunogenetics Laboratory.

2, Yauzskaya Alleya, Moscow, 107564.

Phone: +7 (499) 785-90-72.

tanya00747@gmail.ruАптА. С.АptA. S.

Апт Александр Соломонович, руководитель лаборатории иммуногенетики.

107564, Москва, Яузская аллея, д. 2.

Тел.: +7 (499) 785-90-72.

Aleksandr S. Apt, Head of Immunogenetics Laboratory.

2, Yauzskaya Alleya, Moscow, 107564.

Phone: +7 (499) 785-90-72.

alexapt0151@gmail.comФГБНУ «Центральный НИИ туберкулеза»РоссияCentral Tuberculosis Research InstituteRussian Federation20211201202299125764Copyright © Рубакова Э.И., Кондратьева Т.К., Апт А.С., 20222022Рубакова Э.И., Кондратьева Т.К., Апт А.С.Rubakova E.I., Kondratieva T.K., Аpt A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.tibl-journal.com/jour/article/view/1600

В обзоре приводятся данные из 54 источников литературы. Транскрипционный анализ клеток периферической крови человека позволяет выявить молекулярные механизмы регуляции течения туберкулеза. Особое значение исследователи придают интерферон-индуцируемым генам. При активном туберкулезе, наряду с повышенной экспрессией интерферон-индуцируемых генов, наблюдаются активация генов воспаления в миелоидных клетках и снижение активации генов, определяющих функционирование B- и Т-лимфоцитов. Профиль экспрессии генов соотносится с рентгенологической картиной заболевания у конкретного пациента. Выявлено снижение экспрессии интерферон-индуцируемых генов на фоне успешного лечения туберкулеза. Профиль экспрессии генов, характерный для пациентов с активным туберкулезом, не совпадает с таковым у большинства людей с латентной туберкулезной инфекцией.

The article presents a review of 54 publications. Transcriptional analysis of human peripheral blood cells reveals molecular mechanisms regulating the course of tuberculosis. Researchers put special emphasis on interferon-induced genes. In active tuberculosis along with increased expression of interferon-induced genes, there is the activation of inflammation genes in myeloid cells and decreased activation of genes that determine the function of B- and T-lymphocytes. The gene expression profile correlates with the radiological signs of the disease in a particular patient. Decreased expression of interferon-induced genes against the background of successful tuberculosis treatment was detected. The gene expression profile characteristic of patients with active tuberculosis does not match that of most people with latent tuberculosis infection.

туберкулезэкспрессия геновбиологические маркерыtuberculosisgene expressionbiological markersReferencesApt A. S., Logunova N. N., Kondratieva T. K. Host genetics in susceptibility to and severity of mycobacterial diseases // Tuberculosis (Edinb). – 2017. ‒ Vol. 106. ‒ P. 1-8.Apt A.S., Logunova N.N., Kondratieva T.K. Host genetics in susceptibility to and severity of mycobacterial diseases. Tuberculosis (Edinb.), 2017, vol. 106, pp. 1-8.Berry M. P. R., Graham C. M., McNab F. W. et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis // Nature. ‒ 2010. ‒ Vol. 466. – P. 973-977.Berry M.P.R., Graham C.M., McNab F.W. et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature, 2010, vol. 466, pp. 973-977.Blankley S., Graham C. M., Turneret J. et al. A 380-gene meta-signature of active tuberculosis compared with healthy controls // Eur. Respir J. ‒ 2016. ‒ Vol. 7. ‒ P. 1873-1876.Blankley S., Graham C.M., Turneret J. et al. A 380-gene meta-signature of active tuberculosis compared with healthy controls. Eur. Respir J., 2016, vol. 7, pp. 1873-1876.Blankley S., Graham C. M., Turner J. et al. The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis // PLoS One. – 2016. – Vol. 11, № 10. ‒ Р. 162220.Blankley S., Graham C.M., Turner J. et al. The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis. PLoS One, 2016, vol. 11, no. 10, pp. 162220.Bloom C. I., Graham C. M., Berry M. P. et al. Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy // PLoS One. – 2012. ‒ Vol. 7, № 10. ‒ Р. e46191.Bloom C.I., Graham C.M., Berry M.P. et al. Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. PLoS One, 2012, vol. 7, no. 10, pp. e46191.Bloom C. I., Graham C. M., Berry M. P. et al. Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers // PLoS One. ‒ 2013. ‒ Р. 8, № 8. ‒ Р. e70630.Bloom C.I., Graham C.M., Berry M.P. et al. Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers. PLoS One, 2013, pp. 8, no. 8, pp. e70630.Casanova J. L., Abel L. Genetic dissection of immunity to mycobacteria: the human model // Annu. Rev. Immunol. – 2002. ‒ Vol. 20. ‒ P. 581-620.Casanova J.L., Abel L. Genetic dissection of immunity to mycobacteria: the human model. Annu. Rev. Immunol., 2002, vol. 20, pp. 581-620.Chakravanty S. D., Zhu G., Tsai M. C. et al. Tumor necrosis factor blockade in chronic murine tuberculosis tnhances granulomatous inflammation and disorganizes granulomas in the lungs // Infection. Immunol. – 2008. ‒ Vol. 76. ‒ P. 916-926.Chakravanty S.D., Zhu G., Tsai M.C. et al. Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs. Infection. Immunol., 2008, vol. 76, pp. 916-926.Cliff J. M., Lee J. S., Constantinou N., Cho J. E. et al. Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response // J. Infect Dis. – 2013. ‒ Vol. 207, № 1. ‒ P. 18-29.Cliff J.M., Lee J.S., Constantinou N., Cho J.E. et al. Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response. J. Infect Dis., 2013, vol. 207, no. 1, pp. 18-29.Cliff J. M., Kaufmann S. H., McShane H. et al. The human immune response to tuberculosis and its treatment: a view from the blood // Immunol. Rev. – 2015. ‒ Vol. 264. ‒ P. 88-102.Cliff J.M., Kaufmann S.H., McShane H. et al. The human immune response to tuberculosis and its treatment: a view from the blood. Immunol. Rev., 2015, vol. 264, pp. 88-102.Cooper A. M. Cell-mediated immune responses in tuberculosis // Annu. Rev. Immunol. – 2009. ‒ Vol. 27. ‒ P. 393-422.Cooper A.M. Cell-mediated immune responses in tuberculosis. Annu. Rev. Immunol., 2009, vol. 27, pp. 393-422.Donovan M. L., Schultz T. E., Duke T. J, Blumenthal A. Type I interferons in the pathogenesis of tuberculosis: molecular drivers and immunological consequences // Front. Immunol. ‒ 2017. ‒ Vol. 27 – P. 1-16.Donovan M.L., Schultz T.E., Duke T.J, Blumenthal A. Type I interferons in the pathogenesis of tuberculosis: molecular drivers and immunological consequences. Front. Immunol., 2017, vol. 27, pp. 1-16.Dorhoi A., Iannaccone M., Maertzdorf J. et al. Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease // Front. Immunol. ‒ 2014. ‒ Vol. 5. ‒ P. 1-8.Dorhoi A., Iannaccone M., Maertzdorf J. et al. Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease. Front. Immunol., 2014, vol. 5, pp. 1-8.Dorhoi A., Yeremeev V., Nouailles G. et al. Type I IFN signaling triggers immunopathology in tuberculosis-susceptible mice by modulating lung phagocyte dynamics // Eur. J. Immunol. ‒ 2014. ‒ Vol. 44, № 8. ‒ P. 2380-2393.Dorhoi A., Yeremeev V., Nouailles G. et al. Type I IFN signaling triggers immunopathology in tuberculosis-susceptible mice by modulating lung phagocyte dynamics. Eur. J. Immunol., 2014, vol. 44, no. 8, pp. 2380-2393.Eruslanov E. B., Lyadova I. V., Kondratieva T. K. et al. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice // Infect. Immun. – 2005. ‒ Vol. 73, № 3. ‒ P. 1744-1753.Eruslanov E.B., Lyadova I.V., Kondratieva T.K. et al. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infect. Immun., 2005, vol. 73, no. 3, pp. 1744-1753.Esmail H., Lai R. P., Lesosky M. et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography // Nat. Med. – 2016. ‒ Vol. 22 – P. 1090-1093.Esmail H., Lai R.P., Lesosky M. et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nat. Med., 2016, vol. 22, pp. 1090-1093.Esmail H., Lai R. P., Lesosky M. et al. Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis // Proc. Natl. Acad. Sci. U S A. ‒ 2018. ‒ Vol. 115. ‒ P. E964-E973.Esmail H., Lai R.P., Lesosky M. et al. Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis. Proc. Natl. Acad. Sci. USA, 2018, vol. 115, pp. E964-E973.Eum S. Y., Kong J. H., Hong M. S. et al. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB // Chest. ‒ 2010. ‒ Vol. 137, № 1. ‒ P. 122-128.Eum S.Y., Kong J.H., Hong M.S. et al. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB. Chest, 2010, vol. 137, no. 1, pp. 122-128.Goyal S., Klassert T. E., Slevogt H. C-type lectin receptors in tuberculosis: what we know // Med. Microbiol. Immunol. – 2016. ‒ Vol. 205, № 6. ‒ P. 513-535.Goyal S., Klassert T.E., Slevogt H. C-type lectin receptors in tuberculosis: what we know. Med. Microbiol. Immunol., 2016, vol. 205, no. 6, pp. 513-535.Huang C. N., Lee L. N., Ho C. C. et al. High serum level of procalcitonin and sTREM correlated with poor prognosis in pulmonary TB // J. Infect. ‒ 2014. ‒ Vol. 68, № 5. ‒ P. 440-447.Huang C.N., Lee L.N., Ho C.C. et al. High serum level of procalcitonin and sTREM correlated with poor prognosis in pulmonary TB. J. Infect., 2014, vol. 68, no. 5, pp. 440-447.Ishikawa E., Mori D., Yamasaki S. Recognition of mycobacterial lipids by immune receptors // Trends Immunol. – 2017. ‒ Vol. 38, № 1. ‒ P. 66-76.Ishikawa E., Mori D., Yamasaki S. Recognition of mycobacterial lipids by immune receptors. Trends Immunol., 2017, vol. 38, no. 1, pp. 66-76.Jacobsen M. et al. Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis // J. Mol. Med. ‒ 2007. ‒ Vol. 85. ‒ P. 613-621.Jacobsen M. et al. Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis. J. Mol. Med., 2007, vol. 85, pp. 613-621.Jacobsen M. et al. Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosisTB patients // Clin. Microbiol. Infect. – 2011. ‒ Vol. 17. ‒ P. 1323-1331.Jacobsen M. et al. Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosis TB patients. Clin. Microbiol. Infect., 2011, vol. 17, pp. 1323-1331.Kaforou M., Wright V. J., Oni T. et al. Detection of tuberculosis in HIV-infected and uninfected African adults using whole blood RNA expression signatures: a case-control study // PLoS Med. – 2013. ‒ Vol. 10, № 10. ‒ Р. e1001538.Kaforou M., Wright V.J., Oni T. et al. Detection of tuberculosis in HIV-infected and uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med., 2013, vol. 10, no. 10, pp. e1001538.Liu P. T., Stenger S., Tang D. H., Modlin R. L. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin // J. Immunol. ‒ 2007. ‒ Vol. 179, № 4. ‒ P. 2060-2063.Liu P.T., Stenger S., Tang D.H., Modlin R.L. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J. Immunol., 2007, vol. 179, no. 4, pp. 2060-2063.Lowe D. M., Redford P. S., Wilkinson R. J. et al. Neutrophils in tuberculosis: friend or foe // Trends Immunol. ‒ 2012. ‒ Vol. 33, № 1. ‒ P. 14-25.Lowe D.M., Redford P.S., Wilkinson R.J. et al. Neutrophils in tuberculosis: friend or foe. Trends Immunol., 2012, vol. 33, no. 1, pp. 14-25.MacMicking J., Xie Q.W., Nathan C. Nitric oxide and macrophage function // Annu. Rev. Immunol. – 1997. ‒ Vol. 15. ‒ P. 323-350.MacMicking J., Xie Q.W., Nathan C. Nitric oxide and macrophage function. Annu. Rev. Immunol., 1997, vol. 15, pp. 323-350.Maertzdorf J., Ota M., Repsilber D. et al. Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis // PLoS One. ‒ 2011. ‒ Vol. 6, № 10. ‒ Р. e26938.Maertzdorf J., Ota M., Repsilber D. et al. Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis. PLoS One, 2011, vol. 6, no. 10, pp. e26938.Maertzdorf J., Repsilber D., Parid S. K. et al. Human gene expression profiles of susceptibility and resistance in tuberculosis // Genes Immun. – 2011. ‒ Vol. 12, № 1. ‒ P. 15-22.Maertzdorf J., Repsilber D., Parid S.K. et al. Human gene expression profiles of susceptibility and resistance in tuberculosis. Genes Immun., 2011, vol. 12, no. 1, pp. 15-22.Maertzdorf J., Weiner J. 3rd, Mollenkopf H. J. et al. Common patterns and disease-related signatures in tuberculosis and sarcoidosis // Proc. Natl. Acad. Sci. U S A. ‒ 2012. ‒ Vol. 109, № 20. ‒ P. 7853-7858.Maertzdorf J., Weiner J. 3rd, Mollenkopf H.J. et al. Common patterns and disease-related signatures in tuberculosis and sarcoidosis. Proc. Natl. Acad. Sci. USA, 2012, vol. 109, no. 20, pp. 7853-7858.Manca C., Tsenova L. Bergtold A. et al. Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta // Proc. Natl. Acad. Sci. U S A. ‒ 2001. ‒ Vol. 98, № 10. ‒ P. 5752-5757.Manca C., Tsenova L. Bergtold A. et al. Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta. Proc. Natl. Acad. Sci., USA, 2001, vol. 98, no. 10, pp. 5752-5757.Manca C., Tsenova L., Freeman S. et al. Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway // J. Interferon Cytokine Res. – 2005. ‒ Vol. 25, № 11. ‒ P. 694-701.Manca C., Tsenova L., Freeman S. et al. Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway. J. Interferon Cytokine Res., 2005, vol. 25, no. 11, pp. 694-701.Mayer-Barber K. D., Andrade B. B., Oland S. D. et al. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk // Nature. ‒ 2014. ‒ Vol. 511, № 7507. ‒ P. 99-103.Mayer-Barber K.D., Andrade B.B., Oland S.D. et al. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature, 2014, vol. 511, no. 7507, pp. 99-103.McNab F., Mayer-Barber K., Sher A. et al. Type I interferons in infectious disease // Nat. Rev. Immunol. – 2015. ‒ Vol. 15, № 2. ‒ P. 87-103.McNab F., Mayer-Barber K., Sher A. et al. Type I interferons in infectious disease. Nat. Rev. Immunol., 2015, vol. 15, no. 2, pp. 87-103.Michalska A., Blaszczyk K., Wesoly J. et al. A positive feedback amplifier circuit that regulates interferon (IFN)-stimulated gene expression and controls type I and type II IFN responses // Front. Immunol. – 2018. ‒ Vol. 9. ‒ P. e1135.Michalska A., Blaszczyk K., Wesoly J. et al. A positive feedback amplifier circuit that regulates interferon (IFN)-stimulated gene expression and controls type I and type II IFN responses. Front. Immunol., 2018, vol. 9, pp. e1135.MinDeng, Xiao-Dong Lv, Zhi-Xian Fang et al. The blood transcriptional signature for active and latent tuberculosis // Infect. Drug Resist. – 2019. ‒ Vol. 12. ‒ P. 321-328.MinDeng, Xiao-Dong Lv, Zhi-Xian Fang et al. The blood transcriptional signature for active and latent tuberculosis. Infect. Drug Resist., 2019, vol. 12, pp. 321-328.Mishra A., Akhtar S., Jagannath C., Khan A. Pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immune pathogenesis: Emerging concepts and perspectives // Mol. Immunol. – 2017. ‒ Vol. 87. ‒ P. 240-248.Mishra A., Akhtar S., Jagannath C., Khan A. Pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immune pathogenesis: Emerging concepts and perspectives. Mol. Immunol., 2017, vol. 87, pp. 240-248.Mistry R., Cliff J. M., Clayton C. L. et al. Gene expression patterns in whole blood identity subjects at risk for recurrent tuberculosis // J. Infect Dis. – 2007. ‒ Vol. 195, № 3. ‒ Р. 357-365.Mistry R., Cliff J.M., Clayton C.L. et al. Gene expression patterns in whole blood identity subjects at risk for recurrent tuberculosis. J. Infect Dis., 2007, vol. 195, no. 3, pp. 357-365.Moreira-Teixeira L., Mayer-Barber K., Sher A., O'Garra A. Type I interferons in tuberculosis: Foe and occasionally friend // J. Exp. Med. – 2018. ‒ Vol. 215, № 5. ‒ P. 1273-1285.Moreira-Teixeira L., Mayer-Barber K., Sher A., O'Garra A. Type I interferons in tuberculosis: Foe and occasionally friend. J. Exp. Med., 2018, vol. 215, no. 5, pp. 1273-1285.Naranbhai V., Hill A. V., Abdool Karim S. S. et al. Ratio of monocytes to lymphocytes in peripheral blood identifies adults at risk of incident tuberculosis among HIV-infected adults initiating antiretroviral therapy // J. Infect. Dis. – 2014. ‒ Vol. 209, № 4. ‒ P. 500-509.Naranbhai V., Hill A.V., Abdool Karim S.S. et al. Ratio of monocytes to lymphocytes in peripheral blood identifies adults at risk of incident tuberculosis among HIV-infected adults initiating antiretroviral therapy. J. Infect. Dis., 2014, vol. 209, no. 4, pp. 500-509.North R. J., Jung Y. J. Immunity to tuberculosis // Annu. Rev. Immunol. ‒ 2004. ‒ Vol. 22. ‒ P. 599-623.North R.J., Jung Y.J. Immunity to tuberculosis. Annu. Rev. Immunol., 2004, vol. 22, pp. 599-623.O’Garra A., Redford P. S., McNab F. W. et al. The immune response in tuberculosis // Annu. Rev. Immunol. – 2013. ‒ Vol. 31. ‒ P. 475-527.O’Garra A., Redford P.S., McNab F.W. et al. The immune response in tuberculosis. Annu. Rev. Immunol., 2013, vol. 31, pp. 475-527.Ordway D., Henao-Tamayo M., Harton M. et al. The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation // J. Immunol. – 2007. ‒ Vol. 179, № 1. ‒ P. 522-531.Ordway D., Henao-Tamayo M., Harton M. et al. The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation. J. Immunol., 2007, vol. 179, no. 1, pp. 522-531.Orme I. M., Robinson R. T., Cooper A. M. The balance between protective and pathogenic immune responses in the TB-infected lung // Nat. Immunol. – 2015. ‒ Vol. 16. ‒ P. 57-63.Orme I.M., Robinson R.T., Cooper A.M. The balance between protective and pathogenic immune responses in the TB-infected lung. Nat. Immunol., 2015, vol. 16, pp. 57-63.Ottenhoff T. H., Dass R. H., Yang N. et al. Genome-wide expression profiling identifies type 1 interferon response pathways in active tuberculosis // PLOS One. ‒ 2012. ‒ Vol. 7. ‒ P. e45839.Ottenhoff T.H., Dass R.H., Yang N. et al. Genome-wide expression profiling identifies type 1 interferon response pathways in active tuberculosis. PLOS One, 2012, vol. 7, pp. e45839.Penn-Nicholson A., Mbandi S. K., Thompson E. et al. RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response //Sci. Reports. – 2020. ‒ Vol. 10. ‒ P. e8629Penn-Nicholson A., Mbandi S.K., Thompson E. et al. RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response. Sci. Reports, 2020, vol. 10, pp. e8629Sakai S., Kauffman K. D., Sallin M. A. et al. CD4 T cell-derived IFN-gamma plays a minimal role in control of pulmonary Mycobacterium tuberculosis infection and must be actively repressed by PD-1 to prevent lethal disease // PLoS Pathog. – 2016. ‒ Vol. 12, № 5. ‒ Р. e1005667.Sakai S., Kauffman K.D., Sallin M.A. et al. CD4 T cell-derived IFN-gamma plays a minimal role in control of pulmonary Mycobacterium tuberculosis infection and must be actively repressed by PD-1 to prevent lethal disease. PLoS Pathog., 2016, vol. 12, no. 5, pp. e1005667.Scriba T. J., Fiore-Gartland A., Penn-Nicholson A. Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial // Lancet Infect Dis. – 2021. – Vol. 21, № 3. – P. 354-365.Scriba T.J., Fiore-Gartland A., Penn-Nicholson A. Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial. Lancet Infect Dis., 2021, vol. 21, no. 3, pp. 354-365.Sen Wang, Lei He, Jing Wu et al. Transcriptional profiling of human peripheral blood mononuclear cells identifies diagnostic biomarkers that distinguish active and latent tuberculosis // Front. Immunol. – 2019. – Vol. 10. – P. 2948.Sen Wang, Lei He, Jing Wu et al. Transcriptional profiling of human peripheral blood mononuclear cells identifies diagnostic biomarkers that distinguish active and latent tuberculosis. Front. Immunol., 2019, vol. 10, pp. 2948.Singhania A., Wilkinson R. J., Rodrigue M. et al. Transcriptomics in TB: the immune response and diagnosis // Nat. Immunol. – 2018. – Vol. 11. – P. 1159-1168.Singhania A., Wilkinson R.J., Rodrigue M. et al. Transcriptomics in TB: the immune response and diagnosis. Nat. Immunol., 2018, vol. 11, pp. 1159-1168.Singhania A., Verma R., Graham C. M. et al. A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis // Nature Communication. – 2018. – Vol. 9. – P. e:2308.Singhania A., Verma R., Graham C.M. et al. A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis. Nature Communications, 2018, vol. 9, pp. e:2308.Sweeney T. E., Braviak L., Tato C. M., Khatri P. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis // Lancet Respir. Med. – 2016. – Vol. 4, № 3. – P. 213-224.Sweeney T.E., Braviak L., Tato C.M., Khatri P. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir. Med., 2016, vol. 4, no. 3, pp. 213-224.Szeliga J., Daniel D. S., Yang C. H. et al. Granulocyte-macrophage colony stimulating factor-mediated innate responses in tuberculosis // Tuberculosis (Edinb.) – 2008. – Vol. 88, № 1 – P. 7-20.Szeliga J., Daniel D.S., Yang C.H. et al. Granulocyte-macrophage colony stimulating factor-mediated innate responses in tuberculosis. Tuberculosis (Edinb.), 2008, vol. 88, no. 1, pp. 7-20.Zak D. E., Penn-Nicholson A., Scriba T. J. et al. A blood RNA signature for tuberculosis disease risk: a prospective cohort study // Lancet. – 2016. – Vol. 387. – P. 2312-2322.Zak D.E., Penn-Nicholson A., Scriba T.J. et al. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet, 2016, vol. 387, pp. 2312-2322.

The authors declare that there are no conflicts of interest present.