The proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages

Cristina L. Vázquez, Angela Rodgers, Susanne Herbst, Stephen Coade, Achim Gronow, Carlos A. Guzman, Mark S. Wilson, Makoto Kanzaki, Anders Nykjaer, Maximiliano G. Gutierrez

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Article number29332
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Jul 8

ASJC Scopus subject areas

  • General

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