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Using global proteomics to discover new anti-TB pathways of macrophages

日期: 2019-03-28
题目:Using global proteomics to discover new anti-TB pathways of macrophages
演讲人:Jeffery Cox, Ph.D
C.H. Li Endowed Chair of Biochemistry and Endocrinology
Faculty Director,
Center for Emerging and Neglected Diseases
Professor of Molecular & Cell Biology
UC Berkeley
Macrophages are innate immune cells critical for controlling many bacterial infections, including tuberculosis. However, many pathogens, including Mycobacterium tuberculosis, can hijack these cells and use them as sites of replication. The pathways that control intracellular bacterial growth and how they are manipulated by pathogens are not well understood. We have utilized cutting-edge mass spectrometry techniques to comprehensively probe the interactions between macrophages and three intracellular bacterial pathogens, M. tuberculosis, Salmonella and Listeria. Monitoring both host-microbe protein-protein interactions and host post-translational modification has uncovered new targets and pathways that influence antibacterial responses and bacterial growth. Our results revealed thousands of ubiquitylation and phosphorylation events that occur early after infection, most of which were previously unknown. Unlike transcriptional responses to bacterial infection, which are largely monotonic, our results reveal a surprising diversity in ubiquitin-mediated responses to each pathogen. Likewise, using well-defined attenuated bacterial mutants revealed a remarkable ability of macrophages to discriminate virulent from non-virulent bacteria, suggesting macrophages can integrate information about the nature of the engulfed bacteria and elicit unique responses. These studies have uncovered a unique mechanism by which bacterial pathogens suppress antibacterial immune responses by activating inappropriate antiviral innate responses.