Response to interferons and antibacterial innate immunity in the absence of tyrosine-phosphorylated STAT1.
EMBO Rep
; 17(3): 367-82, 2016 Mar.
Article
in En
| MEDLINE
| ID: mdl-26882544
ABSTRACT
Signal transducer and activator of transcription 1 (STAT1) plays a pivotal role in the innate immune system by directing the transcriptional response to interferons (IFNs). STAT1 is activated by Janus kinase (JAK)-mediated phosphorylation of Y701. To determine whether STAT1 contributes to cellular responses without this phosphorylation event, we generated mice with Y701 mutated to a phenylalanine (Stat1(Y701F)). We show that heterozygous mice do not exhibit a dominant-negative phenotype. Homozygous Stat1(Y701F) mice show a profound reduction in Stat1 expression, highlighting an important role for basal IFN-dependent signaling. The rapid transcriptional response to type I IFN (IFN-I) and type II IFN (IFNγ) was absent in Stat1(Y701F) cells. Intriguingly, STAT1Y701F suppresses the delayed expression of IFN-I-stimulated genes (ISG) observed in Stat1(-/-) cells, mediated by the STAT2/IRF9 complex. Thus, Stat1(Y701F) macrophages are more susceptible to Legionella pneumophila infection than Stat1(-/-) macrophages. Listeria monocytogenes grew less robustly in Stat1(Y701F) macrophages and mice compared to Stat1(-/-) counterparts, but STAT1Y701F is not sufficient to rescue the animals. Our studies are consistent with a potential contribution of Y701-unphosphorylated STAT1 to innate antibacterial immunity.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Legionnaires' Disease
/
Protein Processing, Post-Translational
/
Interferons
/
STAT1 Transcription Factor
/
Immunity, Innate
/
Listeriosis
Limits:
Animals
Language:
En
Journal:
EMBO Rep
Journal subject:
BIOLOGIA MOLECULAR
Year:
2016
Type:
Article
Affiliation country:
Austria