MACROAUTOPHAGY AND ITS ROLE IN THE PATHOGENESIS OF TUBERCULOSIS

DOI: 10.22138/2500-0918-2021-18-2-95-105

D.Yu. Grebnev¹, ², A.V. Osipenko¹, R.V. Ryabov¹,
M.K. Manuilov¹, I.Yu. Maklakova¹, ²

¹ Ural State Medical University, Yekaterinburg, Russian Federation;
² Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation

Abstract. Tuberculosis is a widespread disease worldwide that is caused by various mycobacterium tuberculosis (MTB). The main feature of this pathogen is the ability to persist inside the cells, carrying out phagocytosis. The pathogenesis of tuberculosis includes both inherent and adaptive immunity.The specific role in the genesis of the disease is played by macrophages, which are not only the first line of defense of macroorganism, but also they are habitable environment for MTB. Persistence inside alveolar macrophages is the absolute prerequisite to human disease. Another effector mechanism has come to the scientists’ attention, which could potentially be a kind of «key» in the treatment of mycobacterial infection. This process is called macroautophagy, its feature is the regulated isolation of the pathogen inside macrophages into special phagophores and also the formation of an autophagosome. Then comes the fusion of the autophagosome with the lysosome and intracellular degradation of the pathogen. Meanwhile, MTB has developed strategies to avoid macroautophagy. Here is the list: increased expression of the Eis (enhanced intracellular survival) gene; inhibition of Ras-related protein-Rab-7a; suppression of IFN-γ exposure to interlikin-6 produced by MTB-infected macrophages; and microRNA regulation. All these mechanisms reflect a well-coordinated process of autophagy avoiding. They are potential points to affect combating against MTB. Research objective. To summarize and analyze the data presented in PubMed, eLIBRARY, CyberLeninka databases on macroautophagy as a process that maintains intracellular homeostasis and its potential use against mycobacterial infection. This review also highlighted the factors that mycobacterium use to evade macroautophagy, which contributes to the persistence of this microorganism inside macrophages and complicates the process of recuperation. Materials and methods. The macroautophagy process and its peculiarities in MTB control were the object of study and searches in the PubMed, eLIBRARY, and CyberLeninka databases. We analyzed data presented in the open press for the last 27 years (1994-2020), the inquiry included the pathogenesis of MTB and strategies of MTB evasion of macroautophagy. Results. It was found that macroautophagy can potentially be a component of treatment of mycobacterial infection, but this aspect requires more detailed study. We also examined those strategies that ensure MTB survival inside phagocytic cells. These mechanisms of macroautophagy evasion can be points of application of pathogenetic therapy as well as host targeting therapy.

Keywords: macroautophagy, tuberculosis, immunity, avoidance of autophagy, Eis gene, rab-7a, IL-6, microRNA

There is no conflict of interest.
Contact details of the corresponding author:
Dmitry Yu. Grebnev
dr-grebnev77@mail.ru
Received 20.05.2021г
For citation:
Grebnev D.Yu., Osipenko A.V., Ryabov R.V., Manuilov M.K., Maklakova I.Yu. Macroautophagy and its Role in the Pathogenesis of Tuberculosis. [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2021, Vol. 18, no. 2, pp. 95–109. DOI: 10.22138/2500-0918-2021-18-2-95-109 (In Russ)

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Authors
Dmitry Yu. Grebnev
Ural State Medical University
Dr. Sci. (Med.), Head of the Department of pathological physiology
3 Repin str. Yekaterinburg Russian Federation 620028
Institute of Medical Cell Technologies
Senior researcher
22a Karl Marx str. Yekaterinburg Russian Federation 620026
dr-grebnev77@mail.ru

Arthur V. Osipenko
Ural State Medical University
Dr. Sci. (Med.), Professor, Department of Pathological physiology
3 Repin str. Yekaterinburg Russian Federation 620028
dr-grebnev77@mail.ru

Roman V. Ryabov
Ural State Medical University
Third year medicine and prevention faculty student
3 Repin str. Yekaterinburg Russian Federation 620028
Rrv2903@gmail.com

Mikhail K. Manuilov
Ural State Medical University
Third year medicine and prevention faculty student
3 Repin str. Yekaterinburg Russian Federation 620028
ya.manuilov2012@yandex.ru

Irina Yu. Maklakova
Ural State Medical University
Candidate of Medical Sciences, Associate Professor of the Department of Pathological Physiology
3 Repin St., Yekaterinburg, Russian Federation, 620028
Institute of Medical Cell Technologies
Senior Researcher
22a Karl Marks str. Yekaterinburg Russian Federation, 620026
makliu@mail.ru

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