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dc.contributor.authorVázquez, Cristina L
dc.contributor.authorRodgers, Angela
dc.contributor.authorHerbst, Susanne
dc.contributor.authorCoade, Stephen
dc.contributor.authorGronow, Achim
dc.contributor.authorGuzman, Carlos A
dc.contributor.authorWilson, Mark S
dc.contributor.authorKanzaki, Makoto
dc.contributor.authorNykjaer, Anders
dc.contributor.authorGutierrez, Maximiliano G
dc.date.accessioned2016-07-15T11:06:46Z
dc.date.available2016-07-15T11:06:46Z
dc.date.issued2016
dc.identifier.citationThe proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages. 2016, 6:29332 Sci Repen
dc.identifier.issn2045-2322
dc.identifier.pmid27389464
dc.identifier.doi10.1038/srep29332
dc.identifier.urihttp://hdl.handle.net/10033/616992
dc.description.abstractSorting of luminal and membrane proteins into phagosomes is critical for the immune function of this organelle. However, little is known about the mechanisms that contribute to the spatiotemporal regulation of this process. Here, we investigated the role of the proneurotrophin receptor sortilin during phagosome maturation and mycobacterial killing. We show that this receptor is acquired by mycobacteria-containing phagosomes via interactions with the adaptor proteins AP-1 and GGAs. Interestingly, the phagosomal association of sortilin is critical for the delivery of acid sphingomyelinase (ASMase) and required for efficient phagosome maturation. Macrophages from Sort1(-/-) mice are less efficient in restricting the growth of Mycobacterium bovis BCG and M. tuberculosis. In vivo, Sort1(-/-) mice showed a substantial increase in cellular infiltration of neutrophils in their lungs and higher bacterial burden after infection with M. tuberculosis. Altogether, sortilin defines a pathway required for optimal intracellular mycobacteria control and lung inflammation in vivo.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleThe proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen
refterms.dateFOA2018-06-13T00:52:46Z
html.description.abstractSorting of luminal and membrane proteins into phagosomes is critical for the immune function of this organelle. However, little is known about the mechanisms that contribute to the spatiotemporal regulation of this process. Here, we investigated the role of the proneurotrophin receptor sortilin during phagosome maturation and mycobacterial killing. We show that this receptor is acquired by mycobacteria-containing phagosomes via interactions with the adaptor proteins AP-1 and GGAs. Interestingly, the phagosomal association of sortilin is critical for the delivery of acid sphingomyelinase (ASMase) and required for efficient phagosome maturation. Macrophages from Sort1(-/-) mice are less efficient in restricting the growth of Mycobacterium bovis BCG and M. tuberculosis. In vivo, Sort1(-/-) mice showed a substantial increase in cellular infiltration of neutrophils in their lungs and higher bacterial burden after infection with M. tuberculosis. Altogether, sortilin defines a pathway required for optimal intracellular mycobacteria control and lung inflammation in vivo.


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