title: Different STAT Transcription Complexes Drive Early and Delayed Responses to Type I IFNs.
abstract: IFNs, which transduce pivotal signals through Stat1 and Stat2, effectively suppress the replication of Legionella pneumophila in primary murine macrophages. Although the ability of IFN-γ to impede L. pneumophila growth is fully dependent on Stat1, IFN-αβ unexpectedly suppresses L. pneumophila growth in both Stat1- and Stat2-deficient macrophages. New studies demonstrating that the robust response to IFN-αβ is lost in Stat1-Stat2 double-knockout macrophages suggest that Stat1 and Stat2 are functionally redundant in their ability to direct an innate response toward L. pneumophila. Because the ability of IFN-αβ to signal through Stat1-dependent complexes (i.e., Stat1-Stat1 and Stat1-Stat2 dimers) has been well characterized, the current studies focus on how Stat2 is able to direct a potent response to IFN-αβ in the absence of Stat1. These studies reveal that IFN-αβ is able to drive the formation of a Stat2 and IFN regulatory factor 9 complex that drives the expression of a subset of IFN-stimulated genes, but with substantially delayed kinetics. These observations raise the possibility that this pathway evolved in response to microbes that have devised strategies to subvert Stat1-dependent responses.
authors.affiliation: Department of Microbiology & Immunology, Columbia University, New York, NY 10032 USA.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Abdul-Sater
authors.affiliation: Department of Microbiology, Immunology & Genetics, University of Vienna, Vienna A-1030 Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Majoros
authors.affiliation: Department of Microbiology & Immunology, Columbia University, New York, NY 10032 USA.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Plumlee
authors.affiliation: Division of Vaccine Discovery, La Jolla Inst. for Allergy and Immunology, La Jolla, CA 92037 USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Perry
authors.affiliation: Department of Microbiology & Immunology, Columbia University, New York, NY 10032 USA.
authors.forename: Ai Di
authors.initials: AD
authors.lastname: Gu
authors.affiliation: Department of Microbiology & Immunology, Columbia University, New York, NY 10032 USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Lee
authors.affiliation: Division of Vaccine Discovery, La Jolla Inst. for Allergy and Immunology, La Jolla, CA 92037 USA.
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
authors.affiliation: Department of Microbiology, Immunology & Genetics, University of Vienna, Vienna A-1030 Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.affiliation: Department of Microbiology & Immunology, Columbia University, New York, NY 10032 USA.|Department of Medicine, Columbia University, New York, NY 10032 USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016952:Legionella pneumophila / Q000276:immunology; D007876:Legionellosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061251:Primary Cell Culture; D055503:Protein Multimerization; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D050795:STAT2 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D007371:Interferon-gamma; D053633:Receptor, Interferon alpha-beta; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C508032:Ifnar1 protein, mouse; C494080:Stat1 protein, mouse; C494085:Stat2 protein, mouse; C494228:Isgf3g protein, mouse