Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen
- University of California, Berkeley, United States
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
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Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogenPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE89184).
Article and author information
Author details
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
© 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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