title: Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling.
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.
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Pitt
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Blankley
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Potempa
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Graham
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Lucia
authors.initials: L
authors.lastname: Moreira-Teixeira
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Finlay W
authors.initials: FW
authors.lastname: McNab
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Ashleigh
authors.initials: A
authors.lastname: Howes
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Stavropoulos
authors.affiliation: Baylor Institute for Immunology Research/ANRS Center for Human Vaccines, INSERM, Dallas, Texas, United States of America.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.affiliation: The Jackson Laboratory for Genomic Medicine, 263 Farmington Ave, Farmington, CT 06030, Connecticut, United States of America.
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.affiliation: Systems Immunology, Benaroya Research Institute, Seattle, Washington, United States of America.|Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.affiliation: Laboratory of Immunoregulation and Infection, The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.|Department of Medicine, NHLI, Imperial College, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: O'Garra
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D060467:Disease Resistance; D005786:Gene Expression Regulation / Q000276:immunology; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology*; D059467:Transcriptome
chemical_list: C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma