Artikel ; Online: Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling.
2017 Band 12, Heft 4, Seite(n) e0174973
Abstract: The causative agent of tuberculosis, Mycobacterium tuberculosis (M. tuberculosis), contains an abundant cell wall glycolipid and a crucial virulence factor, trehalose-6,6'-dimycolate (TDM). TDM causes delay of phagosome maturation and thus promotes ... ...
Abstract | The causative agent of tuberculosis, Mycobacterium tuberculosis (M. tuberculosis), contains an abundant cell wall glycolipid and a crucial virulence factor, trehalose-6,6'-dimycolate (TDM). TDM causes delay of phagosome maturation and thus promotes survival of mycobacteria inside host macrophages by a not fully understood mechanism. TDM signals through the Monocyte-INducible C-type LEctin (Mincle), a recently identified pattern recognition receptor. Here we show that recruitment of Mincle by TDM coupled to immunoglobulin (Ig)G-opsonised beads during Fcγ receptor (FcγR)-mediated phagocytosis interferes with phagosome maturation. In addition, modulation of phagosome maturation by TDM requires SH2-domain-containing inositol polyphosphate 5' phosphatase (SHP-1) and the FcγRIIB, which strongly suggests inhibitory downstream signalling of Mincle during phagosome formation. Overall, our study reveals important mechanisms contributing to the virulence of TDM. |
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Mesh-Begriff(e) | Animals ; Cell Line ; Lectins, C-Type/metabolism ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phagosomes/drug effects ; Phagosomes/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism ; Receptors, IgG/metabolism ; Signal Transduction ; Trehalose/pharmacology |
Chemische Substanzen | Clecsf8 protein, mouse ; Fcgr2b protein, mouse ; Lectins, C-Type ; Membrane Proteins ; Receptors, IgG ; Trehalose (B8WCK70T7I) ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 (EC 3.1.3.48) ; Ptpn6 protein, mouse (EC 3.1.3.48) |
Sprache | Englisch |
Erscheinungsdatum | 2017-04-06 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article |
ZDB-ID | 2267670-3 |
ISSN | 1932-6203 ; 1932-6203 |
ISSN (online) | 1932-6203 |
ISSN | 1932-6203 |
DOI | 10.1371/journal.pone.0174973 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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