Dynamic post-translational modification profiling of M. tuberculosis-infected primary macrophages
- University of California, San Francisco, United States
- University of California, Berkeley, United States
- University of California, San Diego, United States
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.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD015361.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (P01 AI063302)
- Jeffery S Cox
Cystic Fibrosis Foundation (Harry Shwachman Award)
- Jonathan M Budzik
National Institute of Allergy and Infectious Diseases (P01 AI063302)
- Nevan J Krogan
National Institute of General Medical Sciences (P50 GM082250)
- Nevan J Krogan
National Institute of Allergy and Infectious Diseases (U19 AI106754)
- Nevan J Krogan
National Institute of Allergy and Infectious Diseases (U19 AI106754)
- Jeffery S Cox
National Institute of Allergy and Infectious Diseases (DP1 AI124619)
- Jeffery S Cox
National Institute of Allergy and Infectious Diseases (R01 AI120694)
- Jeffery S Cox
National Institute of Allergy and Infectious Diseases (R01 AI120694)
- Nevan J Krogan
National Institute of Allergy and Infectious Diseases (1K08AI146267)
- Jonathan M Budzik
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: An animal use protocol (AUP-2015-11-8096) for mouse use was approved by the Office of Laboratory and Animal Care at the University of California, Berkeley, in adherence with guidelines from the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.
Copyright
© 2020, Budzik et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dynamic post-translational modification profiling of M. tuberculosis-infected primary macrophages
eLife 9:e51461.
https://doi.org/10.7554/eLife.51461
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