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, emer ging 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.