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

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 intracellula...

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Autores principales:	Elisabeth Kernbauer, Verena Maier, Dagmar Stoiber, Birgit Strobl, Christine Schneckenleithner, Veronika Sexl, Ursula Reichart, Boris Reizis, Ulrich Kalinke, Amanda Jamieson, Mathias Müller, Thomas Decker
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dd6c4d46781844aab714b3766c46ac2b
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spelling	oai:doaj.org-article:dd6c4d46781844aab714b3766c46ac2b2021-11-18T06:04:18ZConditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.1553-73661553-737410.1371/journal.ppat.1002763https://doaj.org/article/dd6c4d46781844aab714b3766c46ac2b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22719255/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Signal 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.Elisabeth KernbauerVerena MaierDagmar StoiberBirgit StroblChristine SchneckenleithnerVeronika SexlUrsula ReichartBoris ReizisUlrich KalinkeAmanda JamiesonMathias MüllerThomas DeckerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002763 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Elisabeth Kernbauer Verena Maier Dagmar Stoiber Birgit Strobl Christine Schneckenleithner Veronika Sexl Ursula Reichart Boris Reizis Ulrich Kalinke Amanda Jamieson Mathias Müller Thomas Decker Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.
description	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.
format	article
author	Elisabeth Kernbauer Verena Maier Dagmar Stoiber Birgit Strobl Christine Schneckenleithner Veronika Sexl Ursula Reichart Boris Reizis Ulrich Kalinke Amanda Jamieson Mathias Müller Thomas Decker
author_facet	Elisabeth Kernbauer Verena Maier Dagmar Stoiber Birgit Strobl Christine Schneckenleithner Veronika Sexl Ursula Reichart Boris Reizis Ulrich Kalinke Amanda Jamieson Mathias Müller Thomas Decker
author_sort	Elisabeth Kernbauer
title	Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.
title_short	Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.
title_full	Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.
title_fullStr	Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.
title_full_unstemmed	Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.
title_sort	conditional stat1 ablation reveals the importance of interferon signaling for immunity to listeria monocytogenes infection.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/dd6c4d46781844aab714b3766c46ac2b
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Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection.

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