A Rab20-dependent membrane trafficking pathway controls M. tuberculosis replication by regulating phagosome spaciousness and integrity
journal contributionposted on 2020-10-19, 14:01 authored by Laura Schnettger, Angela Rodgers, Urska Repnik, Rachel P Lai, Gang Pei, Martijn Verdoes, Robert J Wilkinson, Douglas B Young, Maximiliano G Gutierrez
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.
Rab GTPasesRab20macrophagemycobacteriumphagosometuberculosisAnimalsAntigens, BacterialBacterial ProteinsCell Culture TechniquesDisease Models, AnimalEndosomesFemaleHost-Pathogen InteractionsHumansInterferon-gammaMacrophagesMembranesMiceMice, Inbred C57BLMycobacterium tuberculosisPhagosomesProtein TransportRAW 264.7 CellsSequence Analysis, RNASpatio-Temporal AnalysisSputumrab GTP-Binding ProteinsGutierrez FC001092Young FC001222Wilkinson, R FC001218BRF-ackLM-ackImmunology0605 Microbiology1108 Medical Microbiology