1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen

  1. Kevin C Barry
  2. Nicholas T Ingolia  Is a corresponding author
  3. Russell E Vance  Is a corresponding author
  1. University of California, Berkeley, United States
Research Article
  • Cited 15
  • Views 2,268
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Cite this article as: eLife 2017;6:e22707 doi: 10.7554/eLife.22707

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 pathogen Legionella pneumophila. Our results reveal that mRNA superinduction is required for the inducible immune response to a bacterial pathogen.

Article and author information

Author details

  1. Kevin C Barry

    Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1064-5964
  2. Nicholas T Ingolia

    Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    ingolia@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
  3. Russell E Vance

    Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    rvance@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6686-3912

Funding

Howard Hughes Medical Institute

  • Russell E Vance

National Institutes of Health (AI075039 AI063302)

  • Nicholas T Ingolia
  • Russell E Vance

Cancer Research Institute

  • Kevin C Barry
  • Russell E Vance

Burroughs Wellcome Fund

  • Russell E Vance

Fibrolamellar Cancer Foundation

  • Kevin C Barry

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: These studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Care and Use Committee at the University of California, Berkeley.

Reviewing Editor

  1. Christopher K Glass, University of California, San Diego, United States

Publication history

  1. Received: October 26, 2016
  2. Accepted: March 27, 2017
  3. Accepted Manuscript published: April 6, 2017 (version 1)
  4. Version of Record published: April 27, 2017 (version 2)

Copyright

© 2017, Barry et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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