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IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection.
Xiong, Juan; Burkovetskaya, Maria; Karpuk, Nikolay; Kielian, Tammy.
Afiliação
  • Xiong J; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
ASN Neuro ; 4(3)2012 Apr 18.
Article em En | MEDLINE | ID: mdl-22414156
ABSTRACT
Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood-brain barrier permeability. To assess the combined actions of IL-1α and IL-1ß during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared with WT (wild-type) animals. Loss of IL-1RI signalling also dampened the expression of select cytokines and chemokines, concomitant with significant reductions in neutrophil and macrophage infiltrates into the brain. In addition, the opening of astrocyte hemichannels during acute infection was shown to be dependent on IL-1RI activity. Collectively, these results demonstrate that IL-1RI signalling plays a pivotal role in the genesis of immune responses during the acute stage of brain abscess development through S. aureus containment, inflammatory mediator production, peripheral immune cell recruitment, and regulation of astrocyte hemichannel activity. Taken in the context of previous studies with MyD88 (myeloid differentiation primary response gene 88) and TLR2 (Toll-like receptor 2) KO animals, the current report advances our understanding of MyD88-dependent cascades and implicates IL-1RI signalling as a major antimicrobial effector pathway during acute brain-abscess formation.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Abscesso Encefálico / Transdução de Sinais / Receptores Tipo I de Interleucina-1 Limite: Animals Idioma: En Revista: ASN Neuro Assunto da revista: NEUROLOGIA / QUIMICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Abscesso Encefálico / Transdução de Sinais / Receptores Tipo I de Interleucina-1 Limite: Animals Idioma: En Revista: ASN Neuro Assunto da revista: NEUROLOGIA / QUIMICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos