Macroautophagy and its Role in the Pathogenesis of Tuberculosis

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.