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

研究成果: Article査読

18 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号29332
ジャーナルScientific reports
6
DOI
出版ステータスPublished - 2016 7 8

ASJC Scopus subject areas

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