Functional dissection of protein domains involved in the immunomodulatory properties of PE_PGRS33 of Mycobacterium tuberculosis. Issue 3 (7th October 2013)

• Record Type: Journal Article
• Authors: Zumbo, Antonella; Palucci, Ivana; Cascioferro, Alessandro; Sali, Michela; Ventura, Marcello; D'Alfonso, Pamela; Iantomasi, Raffaella; Di Sante, Gabriele; Ria, Francesco; Sanguinetti, Maurizio; Fadda, Giovanni; Manganelli, Riccardo; Delogu, Giovanni
• Is Part Of: Pathogens and disease. Volume 69:Issue 3(2013:Dec.)
• Page Start: 232
• Page End: 239
• Publication Date: 2013-10-07
• Subjects: Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1111/2049-632X.12096
• Languages: English
• ISSNs: 2049-632X

Abstract

<abstract abstract-type="main" id="fim12096-abs-0001"> <title>Abstract</title> <p>PE_PGRSs are a large family of proteins identified in <italic>Mycobacterium tuberculosis</italic> complex and in few other pathogenic mycobacteria. The PE domain of PE_PGRS33 mediates localization of the protein on the mycobacterial cell surface, where the PGRS domain is available to interact with host components. In this study, PE_PGRS33 and its functional deletion mutants were expressed in <italic>M. smegmatis</italic>, and <italic>in vitro</italic> and <italic>in vivo</italic> assays were used to dissect the protein domains involved in the immunomodulatory properties of the protein. We demonstrate that PE_PGRS33‐mediated secretion of TNF‐α by macrophages occurs by extracellular interaction with TLR2. Our results also show that while the PGRS domain of the protein is required for triggering TNF‐α secretion, mutation in the PE domain affects the pro‐inflammatory properties of the protein. These results indicate that PE_PGRS33 is a protein with immunomodulatory activity and that protein stability and localization on the mycobacterial surface can affect these properties.</p> </abstract>