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The proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages.
Vázquez, Cristina L Rodgers, Angela Herbst, Susanne Coade, Stephen Gronow, Achim Guzman, Carlos A Wilson, Mark S Kanzaki, Makoto Nykjaer, Anders Gutierrez, Maximiliano G
Vázquez, Cristina L
Rodgers, Angela
Herbst, Susanne
Coade, Stephen
Gronow, Achim
Guzman, Carlos A
Wilson, Mark S
Kanzaki, Makoto
Nykjaer, Anders
Gutierrez, Maximiliano G
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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.
Citation
The proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages. 2016, 6:29332 Sci Rep
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Article
Language
en
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Series/Report no.
ISSN
2045-2322