Functional dissection of protein domains involved in the immunomodulatory properties of PE_PGRS33 of Mycobacterium tuberculosis

Antonella Zumbo, Ivana Palucci, Alessandro Cascioferro, Michela Sali, Marcello Ventura, Pamela D'Alfonso, Raffaella Iantomasi, Gabriele Di Sante, Francesco Ria, Maurizio Sanguinetti, Giovanni Fadda, Riccardo Manganelli, Giovanni Delogu

Research output: Contribution to journalArticlepeer-review

Abstract

PE_PGRSs are a large family of proteins identified in Mycobacterium tuberculosis 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 M. smegmatis, and in vitro and in vivo 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.

Original languageEnglish
Pages (from-to)232-239
Number of pages8
JournalPathogens and Disease
Volume69
Issue number3
DOIs
Publication statusPublished - 2013

Keywords

  • Mycobacterium tuberculosis
  • PE_PGRS
  • TLR2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Microbiology (medical)
  • Immunology and Microbiology(all)

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