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Functional dissection of protein domains involved in the immunomodulatory properties of PE_PGRS33 of Mycobacterium tuberculosis.
- Source :
-
Pathogens and disease [Pathog Dis] 2013 Dec; Vol. 69 (3), pp. 232-9. Date of Electronic Publication: 2013 Oct 07. - Publication Year :
- 2013
-
Abstract
- PE&#95;PGRSs are a large family of proteins identified in Mycobacterium tuberculosis complex and in few other pathogenic mycobacteria. The PE domain of PE&#95;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&#95;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&#95;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&#95;PGRS33 is a protein with immunomodulatory activity and that protein stability and localization on the mycobacterial surface can affect these properties.<br /> (© 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.)
- Subjects :
- Animals
Antigens, Bacterial chemistry
Antigens, Bacterial genetics
Bacterial Proteins chemistry
Bacterial Proteins genetics
Cell Death genetics
Extracellular Space
Female
Gene Expression
Immunomodulation
Macrophages immunology
Macrophages metabolism
Macrophages microbiology
Membrane Proteins chemistry
Membrane Proteins genetics
Mice
Mice, Knockout
Mutation
Mycobacterium tuberculosis genetics
Mycobacterium tuberculosis metabolism
Protein Binding
Splenomegaly genetics
Splenomegaly metabolism
Splenomegaly pathology
Toll-Like Receptor 2 genetics
Toll-Like Receptor 2 metabolism
Tumor Necrosis Factor-alpha biosynthesis
Antigens, Bacterial metabolism
Bacterial Proteins metabolism
Membrane Proteins metabolism
Mycobacterium tuberculosis immunology
Protein Interaction Domains and Motifs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2049-632X
- Volume :
- 69
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Pathogens and disease
- Publication Type :
- Academic Journal
- Accession number :
- 24106104
- Full Text :
- https://doi.org/10.1111/2049-632X.12096