Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling.

TitleAnalysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling.
Publication TypeJournal Article
Year of Publication2016
AuthorsPitt JM, Blankley S, Potempa K, Graham CM, Moreira-Teixeira L, McNab FW, Howes A, Stavropoulos E, Pascual V, Banchereau J, Chaussabel D, O'Garra A
JournalPLoS One
Volume11
Issue2
Paginatione0150251
Date Published2016
ISSN1932-6203
KeywordsAnimals, Blood Cells, Disease Resistance, Gene Expression Regulation, Interferon Type I, Interferon-gamma, Listeriosis, Lymphocyte Count, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptor, Interferon alpha-beta, Signal Transduction, Spleen, T-Lymphocyte Subsets, Transcription, Genetic, Transcriptome
Abstract

Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set of genes are perturbed in both blood and tissue and that these transcriptional responses are enriched for pathways of the immune response. Further we identified enrichment for both type I and type II interferon (IFN) signaling molecules in the blood and tissues upon infection. Since type I IFN signaling has been reported widely to impair bacterial clearance we examined gene expression from blood and tissues of wild type (WT) and type I IFNαβ receptor-deficient (Ifnar1-/-) mice at the basal level and upon infection with L. monocytogenes. Measurement of the fold change response upon infection in the absence of type I IFN signaling demonstrated an upregulation of specific genes at day 1 post infection. A less marked reduction of the global gene expression signature in blood or tissues from infected Ifnar1-/- as compared to WT mice was observed at days 2 and 3 after infection, with marked reduction in key genes such as Oasg1 and Stat2. Moreover, on in depth analysis, changes in gene expression in uninfected mice of key IFN regulatory genes including Irf9, Irf7, Stat1 and others were identified, and although induced by an equivalent degree upon infection this resulted in significantly lower final gene expression levels upon infection of Ifnar1-/- mice. These data highlight how dysregulation of this network in the steady state and temporally upon infection may determine the outcome of this bacterial infection and how basal levels of type I IFN-inducible genes may perturb an optimal host immune response to control intracellular bacterial infections such as L. monocytogenes.

DOI10.1371/journal.pone.0150251
Custom 1

https://www.ncbi.nlm.nih.gov/pubmed/26918359?dopt=Abstract

Alternate JournalPLoS ONE
PubMed ID26918359
PubMed Central IDPMC4768944
Grant ListMC_U117565642 / / Medical Research Council / United Kingdom
MR/J010723/1 / / Medical Research Council / United Kingdom

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