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Cell Host Microbe. 2017 May 10;21(5):619-628.e5. doi: 10.1016/j.chom.2017.04.004.

A Rab20-Dependent Membrane Trafficking Pathway Controls M. tuberculosis Replication by Regulating Phagosome Spaciousness and Integrity.

Author information

1
Host-Pathogen Interactions In Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
2
Mycobacterial Systems Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
3
Department of Biosciences, University of Oslo, Blindernveien 31, 0371 Oslo, Norway.
4
Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
5
Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
6
Radboud Institute for Molecular Life Sciences (RIMLS), Geert Grooteplein 26/28, Nijmegen 6525 GA, the Netherlands.
7
Host-Pathogen Interactions In Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: max.g@crick.ac.uk.

Abstract

The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication. Rab20 is specifically and significantly upregulated in the sputum of human patients with active tuberculosis. Altogether, we uncover an immune-regulated cellular pathway of defense that promotes maintenance of Mtb within intact membrane-bound compartments for efficient elimination.

KEYWORDS:

Rab GTPases; Rab20; macrophage; mycobacterium; phagosome; tuberculosis

PMID:
28494243
PMCID:
PMC5432432
DOI:
10.1016/j.chom.2017.04.004
[Indexed for MEDLINE]
Free PMC Article

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