2.50
Hdl Handle:
http://hdl.handle.net/10033/616992
Title:
The proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages.
Authors:
Vázquez, Cristina L; Rodgers, Angela; Herbst, Susanne; Coade, Stephen; Gronow, Achim; Guzman, Carlos A; Wilson, Mark S; Kanzaki, Makoto; Nykjaer, Anders; Gutierrez, Maximiliano G
Abstract:
Sorting 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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
The proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages. 2016, 6:29332 Sci Rep
Journal:
Scientific reports
Issue Date:
2016
URI:
http://hdl.handle.net/10033/616992
DOI:
10.1038/srep29332
PubMed ID:
27389464
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorVázquez, Cristina Len
dc.contributor.authorRodgers, Angelaen
dc.contributor.authorHerbst, Susanneen
dc.contributor.authorCoade, Stephenen
dc.contributor.authorGronow, Achimen
dc.contributor.authorGuzman, Carlos Aen
dc.contributor.authorWilson, Mark Sen
dc.contributor.authorKanzaki, Makotoen
dc.contributor.authorNykjaer, Andersen
dc.contributor.authorGutierrez, Maximiliano Gen
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.en
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

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