IL-1β-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKβ

Nat Immunol. 2011 Feb;12(2):144-50. doi: 10.1038/ni.1976. Epub 2010 Dec 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Infections / immunology*
  • Cell Count
  • Cell Growth Processes / genetics
  • Cell Survival / genetics
  • Cells, Cultured
  • Disease Susceptibility
  • Granulocyte-Macrophage Progenitor Cells / immunology
  • Granulocyte-Macrophage Progenitor Cells / metabolism*
  • Granulocyte-Macrophage Progenitor Cells / pathology
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / immunology
  • I-kappa B Kinase / metabolism*
  • Immunity, Innate / genetics
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microarray Analysis
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Neutrophils / pathology
  • Receptors, Interleukin-1 Type I / genetics
  • Up-Regulation / genetics


  • Interleukin-1beta
  • Receptors, Interleukin-1 Type I
  • I-kappa B Kinase
  • Ikbkb protein, mouse

Associated data

  • GEO/GSE25211