Dynamic post-translational modification profiling of Mycobacterium tuberculosis-infected primary macrophages.

Abstract:

:Macrophages are highly plastic cells with critical roles in immunity, cancer, and tissue homeostasis, but how these distinct cellular fates are triggered by environmental cues is poorly understood. To uncover how primary murine macrophages respond to bacterial pathogens, we globally assessed changes in post-translational modifications of proteins during infection with Mycobacterium tuberculosis, a notorious intracellular pathogen. We identified hundreds of dynamically regulated phosphorylation and ubiquitylation sites, indicating that dramatic remodeling of multiple host pathways, both expected and unexpected, occurred during infection. Most of these cellular changes were not captured by mRNA profiling, and included activation of ubiquitin-mediated autophagy, an evolutionarily ancient cellular antimicrobial system. This analysis also revealed that a particular autophagy receptor, TAX1BP1, mediates clearance of ubiquitylated Mtb and targets bacteria to LC3-positive phagophores. These studies provide a new resource for understanding how macrophages shape their proteome to meet the challenge of infection.

journal_name

Elife

journal_title

eLife

authors

Budzik JM,Swaney DL,Jimenez-Morales D,Johnson JR,Garelis NE,Repasy T,Roberts AW,Popov LM,Parry TJ,Pratt D,Ideker T,Krogan NJ,Cox JS

doi

10.7554/eLife.51461

subject

Has Abstract

pub_date

2020-01-17 00:00:00

issn

2050-084X

pii

51461

journal_volume

9

pub_type

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