title: Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen.
abstract: The inducible innate immune response to infection requires a concerted process of gene expression that is regulated at multiple levels. Most global analyses of the innate immune response have focused on transcription induced by defined immunostimulatory ligands, such as lipopolysaccharide. However, the response to pathogens involves additional complexity, as pathogens interfere with virtually every step of gene expression. How cells respond to pathogen-mediated disruption of gene expression to nevertheless initiate protective responses remains unclear. We previously discovered that a pathogen-mediated blockade of host protein synthesis provokes the production of specific pro-inflammatory cytokines. It remains unclear how these cytokines are produced despite the global pathogen-induced block of translation. We addressed this question by using parallel RNAseq and ribosome profiling to characterize the response of macrophages to infection with the intracellular bacterial pathogenLegionella pneumophila. Our results reveal that mRNA superinduction is required for the inducible immune response to a bacterial pathogen.
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Kevin C
authors.identifier: 0000-0003-1064-5964
authors.initials: KC
authors.lastname: Barry
authors.affiliation: Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Nicholas T
authors.identifier: 0000-0002-3395-1545
authors.initials: NT
authors.lastname: Ingolia
authors.affiliation: Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.|Cancer Research Laboratory, University of California, Berkeley, Berkeley, United States.|Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States.
authors.forename: Russell E
authors.identifier: 0000-0002-6686-3912
authors.initials: RE
authors.lastname: Vance
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D016952:Legionella pneumophila / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger
keywords: Legionella pneumophila; immunology; infectious disease; innate immunity; macrophages; microbiology; mouse; ribosome profiling; translation