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Modulations of Macrophage Immune Responses by Mycobacterial PE/PPE Family of Proteins

Volume 6, Issue 3-4, 2015, pp. 207-216
DOI: 10.1615/ForumImmunDisTher.v6.i3-4.100
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ABSTRACT

Mycobacterium tuberculosis (Mtb) is a very successful pathogen possessing a plethora of tactics uniquely tailored to undermine the key macrophage defense system for its own survival and multiplication. Completion of the Mtb genome revealed the presence of two unique, acid rich families of proteins called PE /PPE proteins. Owing to their high abundance and expansion in pathogenic mycobacterial species, their association with the ESAT-6 (ESX) secretion system and constituting 7% of the coding potential of the Mtb genome, they have a great potential to act as virulent factors during mycobacterial pathogenesis. Though initially speculated to play a role in antigenic variation, current assessment of the functions of PE/PPE proteins reveal important and diverse roles during mycobacterial infection. Macrophages are important sentinel cells that arbitrate innate as well as adaptive immune responses. Paradoxically, macrophage anti-mycobacterial immune responses are readily manipulated by Mtb to favor their intracellular survival. Insights into the alteration of macrophage signaling pathways by PE/PPE proteins would offer a better perspective to develop effective anti-TB immunotherapeutics and vaccines. In this review, I discuss the significance of the PE/PPE proteins in the modulation of macrophage effector responses.

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