Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen

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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.

Data availability

The following data sets were generated

(2017) Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE89184).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE89184

Article and author information

Author details

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.

"This ORCID iD identifies the author of this article:" 0000-0003-1064-5964
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.
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.

"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.

Copyright

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.