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

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.