IL-1ß-driven neutrophilia preserves antibacterial defense in the absence of the kinase IKKß.
Nat Immunol
; 12(2): 144-50, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21170027
ABSTRACT
Transcription factor NF-κB and its activating kinase IKKß are associated with inflammation and are believed to be critical for innate immunity. Despite the likelihood of immune suppression, pharmacological blockade of IKKß-NF-κB has been considered as a therapeutic strategy. However, we found neutrophilia in mice with inducible deletion of IKKß (Ikkß(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 Ikkß(Δ) mice normalized blood cellularity and prevented neutrophil-driven inflammation. However, Ikkß(Δ)Il1r1(-/-) mice, unlike Ikkß(Δ) mice, were highly susceptible to bacterial infection, which indicated that signaling via IKKß-NF-κB or IL-1R1 can maintain antimicrobial defenses in each other's absence, whereas inactivation of both pathways severely compromises innate immunity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções Bacterianas
/
Quinase I-kappa B
/
Interleucina-1beta
/
Células Progenitoras de Granulócitos e Macrófagos
/
Neutrófilos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article