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Type of publication: Journal Article
Type of document: Full Paper

Year: 2012

Authors: Kernbauer, E; Maier, V; Stoiber, D; Strobl, B; Schneckenleithner, C; Sexl, V; Reichart, U; Reizis, B; Kalinke, U; Jamieson, A; Müller, M; Decker, T

Title: Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.

Source: PLoS Pathog. 2012; 8(6):e1002763

Authors Vetmeduni Vienna:

Müller Mathias
Reichart Ursula
Schneckenleithner Christine
Sexl Veronika
Strobl Birgit

Vetmed Research Units
Biomodels Austria
Institute of Animal Breeding and Genetics
Institute of Pharmacology and Toxicology

Project(s): Austromouse - Austrian Network for Functional Mouse Genomics

Signal transducer and activator of transcription 1 (Stat1) is a key player in responses to interferons (IFN). Mutations of Stat1 cause severe immune deficiencies in humans and mice. Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellular bacterial pathogen Listeria monocytogenes (Lm). Cell type-restricted ablation of the Stat1 gene in naïve animals revealed unique roles in three cell types: macrophage Stat1 signaling protected against lethal Lm infection, whereas Stat1 ablation in dendritic cells (DC) did not affect survival. T lymphocyte Stat1 reduced survival. Type I IFN (IFN-I) signaling in T lymphocytes reportedly weakens innate resistance to Lm. Surprisingly, the effect of Stat1 signaling was much more pronounced, indicating a contribution of Stat1 to pathways other than the IFN-I pathway. In stark contrast, Stat1 activity in both DC and T cells contributed positively to secondary immune responses against Lm in immunized animals, while macrophage Stat1 was dispensable. Our findings provide the first genetic evidence that Stat1 signaling in different cell types produces antagonistic effects on innate protection against Lm that are obscured in mice with complete Stat1 deficiency. They further demonstrate a drastic change in the cell type-dependent Stat1 requirement for memory responses to Lm infection.

Keywords Pubmed: Adoptive Transfer
Dendritic Cells/immunology
Dendritic Cells/metabolism
Dendritic Cells/microbiology
Flow Cytometry
Immunity, Innate/genetics
Immunity, Innate/immunology*
Immunologic Memory/genetics
Immunologic Memory/immunology
Interferon Type I/immunology*
Listeria monocytogenes/immunology
Mice, Inbred C57BL
Mice, Knockout
Real-Time Polymerase Chain Reaction
STAT1 Transcription Factor/genetics
STAT1 Transcription Factor/immunology*
Signal Transduction/genetics
Signal Transduction/immunology*

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