TY - JOUR
T1 - Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection
AU - Kernbauer, Elisabeth
AU - Maier, Verena
AU - Stoiber, Dagmar
AU - Strobl, Birgit
AU - Schneckenleithner, Christine
AU - Sexl, Veronika
AU - Reichart, Ursula
AU - Reizis, Boris
AU - Kalinke, Ulrich
AU - Jamieson, Amanda
AU - Müller, Mathias
AU - Decker, Thomas
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Adoptive Transfer
KW - Animals
KW - Dendritic Cells/immunology
KW - Flow Cytometry
KW - Immunity, Innate/genetics
KW - Immunologic Memory/genetics
KW - Interferon Type I/immunology
KW - Listeria monocytogenes/immunology
KW - Listeriosis/genetics
KW - Macrophages/immunology
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Real-Time Polymerase Chain Reaction
KW - STAT1 Transcription Factor/genetics
KW - Signal Transduction/genetics
KW - T-Lymphocytes/immunology
UR - http://www.scopus.com/inward/record.url?scp=84864047369&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1002763
DO - 10.1371/journal.ppat.1002763
M3 - Journal article
C2 - 22719255
SN - 1553-7366
VL - 8
SP - e1002763
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 6
M1 - e1002763
ER -