Article ; Online: Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling.
2017 Volume 12, Issue 4, Page(s) 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. |
---|---|
MeSH term(s) | 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 |
Chemical Substances | 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) |
Language | English |
Publishing date | 2017-04-06 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 2267670-3 |
ISSN | 1932-6203 ; 1932-6203 |
ISSN (online) | 1932-6203 |
ISSN | 1932-6203 |
DOI | 10.1371/journal.pone.0174973 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.