Immunomodulatory Role of Mycobacterial PE/PPE Family of Proteins

Abstract

Mycobacterium tuberculosis (M.tb) is an adept pathogen possessing unique strategies to exploit and corrupt the very core defense systems designed to curb its own survival and multiplication. Comparative analysis of mycobacterial genomes indicate that the pathogenic mycobacterium have acquired a multitude of genes which play important roles in modulating protective host-cell signaling that are triggered in response to an infection. Therefore, defining the "set of genes" expressed by intracellular pathogens as well as understanding modulations of host-signaling pathways during infection is extremely crucial to devise successful clinical intervention against the development of disease. The unique PE/PPE proteins, which constitute about 10% of coding capacity of M.tb genome, owing to their high abundance and expansion in pathogenic mycobacterial species warrants a better understanding of their role in mycobacterial pathogenesis. The PE/PPE families have been thought to play important roles in generating antigenic variation and immune evasion. Although a comprehensive understanding of their role is yet to be fully understood, emerging evidence supports a role of PE/PPE proteins at multiple levels of infectious process. This review delineates the importance of these proteins in the modulation of macrophage immune effector responses, as well as importance of these proteins in clinical manifestations of TB.

The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

“…Macrophages are primarily efficient in clearing pathogens; however, M.tb can survive intracellularly within the niche of macrophage itself. M.tb has evolved various mechanisms that allow it to hijack the process of phagosome-lysosome fusion, inhibit acidification of phagosome, suppress autophagy and apoptosis pathways used by macrophage for the clearance of pathogens [ 4 , 5 , 6 , 7 ]. M.tb overpowers the extremely microbicidal nature presented within the macrophages through a multifaceted and complex interplay between its proteins and host immune responses [ 8 , 9 ].…”

Prediction of Certain Well-Characterized Domains of Known Functions within the PE and PPE Proteins of Mycobacteria

“…The PE and PPE genes were mostly arranged in a unique regulon with the PE genes located upstream to the PPE genes and scattered throughout the genome [ 18 ]. The PE and PPE genes are known to be present in pathogenic and non-pathogenic mycobacteria but have not yet been identified in non-mycobacterial species [ 19 , 20 , 21 ]. A strong evolutionary selection for PE and PPE proteins in the pathogenic mycobacteria has been reported since their expansion is linked to the ESAT-6 gene clusters that has role in immuno-pathogenesis [ 22 ].…”