title: IL-1β-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKβ.
abstract: Transcription factor NF-κB and its activating kinase IKKβ are associated with inflammation and are believed to be critical for innate immunity. Despite the likelihood of immune suppression, pharmacological blockade of IKKβ-NF-κB has been considered as a therapeutic strategy. However, we found neutrophilia in mice with inducible deletion of IKKβ (Ikkβ(Δ) mice). These mice had hyperproliferative granulocyte-macrophage progenitors and pregranulocytes and a prolonged lifespan of mature neutrophils that correlated with the induction of genes encoding prosurvival molecules. Deletion of interleukin 1 receptor 1 (IL-1R1) in Ikkβ(Δ) mice normalized blood cellularity and prevented neutrophil-driven inflammation. However, Ikkβ(Δ)Il1r1(-/-) mice, unlike Ikkβ(Δ) mice, were highly susceptible to bacterial infection, which indicated that signaling via IKKβ-NF-κB or IL-1R1 can maintain antimicrobial defenses in each other's absence, whereas inactivation of both pathways severely compromises innate immunity.
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. lichunghsu@ntu.edu.tw
authors.forename: Li-Chung
authors.initials: LC
authors.lastname: Hsu
authors.forename: Thomas
authors.initials: T
authors.lastname: Enzler
authors.forename: Jun
authors.initials: J
authors.lastname: Seita
authors.forename: Anjuli M
authors.initials: AM
authors.lastname: Timmer
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Lee
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Lai
authors.forename: Guann-Yi
authors.initials: GY
authors.lastname: Yu
authors.forename: Liang-Chuan
authors.initials: LC
authors.lastname: Lai
authors.forename: Vladislav
authors.initials: V
authors.lastname: Temkin
authors.forename: Ursula
authors.initials: U
authors.lastname: Sinzig
authors.forename: Thiha
authors.initials: T
authors.lastname: Aung
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D002452:Cell Count; D048708:Cell Growth Processes / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D004198:Disease Susceptibility; D055014:Granulocyte-Macrophage Progenitor Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate / Q000235:genetics; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse