Analysis of transcriptional signatures in response to listeria monocytogenes infection reveals temporal changes that result from type i interferon signaling

Jonathan M. Pitt, Simon Blankley, Krzysztof Potempa, Christine M. Graham, Lucia Moreira-Teixeira, Finlay W. McNab, Ashleigh Howes, Evangelos Stavropoulos, Virginia Pascual, Jacques Banchereau, Damien Chaussabel, Anne O'Garra

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 toWT 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.

Original languageEnglish
Article numbere0150251
JournalPLoS One
Volume11
Issue number2
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

Fingerprint

Listeria
Listeriosis
Listeria monocytogenes
interferons
Interferons
Gene expression
Genes
Interferon Type I
Blood
Tissue
Infection
infection
mice
Interferon alpha-beta Receptor
gene expression
blood
Gene Expression
Bacterial Infections
bacterial infections
Interferon-gamma

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Analysis of transcriptional signatures in response to listeria monocytogenes infection reveals temporal changes that result from type i interferon signaling. / Pitt, Jonathan M.; Blankley, Simon; Potempa, Krzysztof; Graham, Christine M.; Moreira-Teixeira, Lucia; McNab, Finlay W.; Howes, Ashleigh; Stavropoulos, Evangelos; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; O'Garra, Anne.

In: PLoS One, Vol. 11, No. 2, e0150251, 01.02.2016.

Research output: Contribution to journalArticle

Pitt, 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 2016, 'Analysis of transcriptional signatures in response to listeria monocytogenes infection reveals temporal changes that result from type i interferon signaling', PLoS One, vol. 11, no. 2, e0150251. https://doi.org/10.1371/journal.pone.0150251
Pitt, Jonathan M. ; Blankley, Simon ; Potempa, Krzysztof ; Graham, Christine M. ; Moreira-Teixeira, Lucia ; McNab, Finlay W. ; Howes, Ashleigh ; Stavropoulos, Evangelos ; Pascual, Virginia ; Banchereau, Jacques ; Chaussabel, Damien ; O'Garra, Anne. / Analysis of transcriptional signatures in response to listeria monocytogenes infection reveals temporal changes that result from type i interferon signaling. In: PLoS One. 2016 ; Vol. 11, No. 2.
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