PE_PGRS30 of Mycobacterium tuberculosis mediates suppression of proinflammatory immune response in macrophages through its PGRS and PE domains

• Published in: Microbes and infection Vol. 18; no. 9; pp. 536 - 542
• Main Authors: Chatrath, Shweta, Gupta, Vineet Kumar, Dixit, Aparna, Garg, Lalit C.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2016
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cell Line; Cytokines - metabolism; Host immune response; Host-Pathogen Interactions; Humans; Immune Evasion; Immune Tolerance; Macrophages - drug effects; Macrophages - immunology; Macrophages - microbiology; Mycobacterium smegmatis - genetics; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - metabolism; PE_PGRS proteins; Plasmids; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Virulence Factors - genetics; Virulence Factors - metabolism; Mycobacterium tuberculosis; PE_PGRS proteins; Host immune response
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2016.04.004

The success of Mycobacterium tuberculosis as a pathogen relies on its ability to survive inside macrophages and evade host immune mechanisms. M. tuberculosis employs multiple strategies to confer resistance against immune system including inhibition of phago-lysosomal fusion, modulation of cytokine responses and granuloma formation. PE_PGRS proteins, uniquely present in pathogenic mycobacteria, are cell surface molecules that are suggested to interact with host cells. PE_PGRS proteins have also been implicated in its pathogenesis. In the present study, immuno-regulatory property of Rv1651c-encoded PE_PGRS30 protein was explored. Infection of PMA-differentiated human THP-1 macrophages with Mycobacterium smegmatis harbouring pVV1651c resulted in reduced production of IL-12, TNF-α and IL-6, as compared to infection with M. smegmatis harbouring the control plasmid pVV16. No differential effect was observed on bacterial persistence inside macrophages or on macrophage mortality upon infection with the two recombinant strains. Infection of THP-1 macrophages with recombinant M. smegmatis expressing deletion variants of PE_PGRS30 indicated that anti-inflammatory function of the protein is possessed by its PGRS and PE domains while the C-terminal domain, when expressed alone, displayed antagonistic effect in terms of TNF-α secretion. These results suggest that PE_PGRS30 interferes with macrophage immune functions important for activation of adaptive T-cell responses.