Macrophages play a critical role in clearance of cytosolic pathogens.
Autophagy functions at the intersection of antimicrobial innate immunity and protein
quality control; however, the impacts of infection and autophagy on shaping the
macrophage proteome are poorly understood. Here, we describe a deep multi-
dimensional proteomic analysis of primary murine macrophages infected with
Shigella flexneri (S.flexneri). Tandem mass tagging (TMT) revealed dynamic
genotype- and infection-dependent differences in host and pathogen proteins,
phosphorylation and ubiquitination. These data catalogue the complex circuitry
connecting autophagy, inflammatory signaling and the oxidative stress response.
Loss of the autophagy gene Atg16l1 induced basal oxidative stress, activated the
compensatory glutathione biosynthetic machinery, and enhanced clearance of
S.flexneri. Pathogen clearance was similarly enhanced in wild type macrophages
upon pharmacological inhibition of cysteine import. Our study provides a resource for
innate immunity research and reveals that ATG16L1 dampens antimicrobial
immunity by regulating oxidative stress.
[doi:10.25345/C5RH9X]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: shigella flexneri ; mus musculus ; tmt multiplexing ; quantitative mass spectrometry ; multiplexed proteomics ; autophagy ; macrophages ; oxidative stress
Principal Investigators: (in alphabetical order) |
Aditya Murthy, Genentech, United States Donald Kirkpatrick, Genentech, United States |
Submitting User: | hinklet |
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