Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling.
Patin EC, Geffken AC, Willcocks S, Leschczyk C, Haas A, Nimmerjahn F, Lang R, Ward TH, Schaible UE (2017)
Publication Status: Published
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 12
Pages Range: e0174973
Journal Issue: 4
DOI: 10.1371/journal.pone.0174973
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.
Authors with CRIS profile
Falk Nimmerjahn
Lehrstuhl für Genetik
Roland Lang
Professur für Angeborene Immunität und Pathogenerkennung
Involved external institutions
London School of Hygiene and Tropical Medicine
United Kingdom (GB)
Forschungszentrum Borstel - Leibniz-Zentrum für Medizin und Biowissenschaften / Research Center Borstel - Leibniz-Center for Medicine and Biosciences
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
United Kingdom (GB)
Forschungszentrum Borstel - Leibniz-Zentrum für Medizin und Biowissenschaften / Research Center Borstel - Leibniz-Center for Medicine and Biosciences
Germany (DE)
Rheinische Friedrich-Wilhelms-Universität Bonn
Germany (DE)
How to cite
APA:
Patin, E.C., Geffken, A.C., Willcocks, S., Leschczyk, C., Haas, A., Nimmerjahn, F.,... Schaible, U.E. (2017). Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling. PLoS ONE, 12(4), e0174973. https://doi.org/10.1371/journal.pone.0174973
MLA:
Patin, Emmanuel C., et al. "Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling." PLoS ONE 12.4 (2017): e0174973.
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