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

eLife

Trevor J Parry¹  Danielle L Swaney²  Nevan J Krogan³  Nicholas E Garelis³  Lauren M Popov³  Trey Ideker⁴  Allison W Roberts⁴  Jeffrey R Johnson⁴  David Jimenez-Morales⁵  Dexter Pratt⁵  Teresa Repasy⁵  Jonathan M Budzik⁶  Jeffery S Cox⁷ 

[1]Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, United States

[2]Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

[3]Gladstone Institutes, San Francisco, United States

[4]Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, United States

[5]Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States

[6]Department of Medicine, University of California, San Francisco, San Francisco, United States

[7]Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

关键词: tuberculosis;    macrophage;    post-translational modification;    proteomics;    autophagy;   

DOI  :  10.7554/eLife.51461

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown