Downregulation of the Na/K-ATPase pump by leptospiral glycolipoprotein activates the NLRP3 inflammasome.
J Immunol
; 188(6): 2805-14, 2012 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-22323544
ABSTRACT
Leptospira interrogans is responsible for a zoonotic disease known to induce severe kidney dysfunction and inflammation. In this work, we demonstrate that L. interrogans induces NLRP3 inflammasome-dependent secretion of IL-1ß through the alteration of potassium transport in bone marrow-derived macrophages. Lysosome destabilization also contributed to the IL-1ß production upon stimulation with live, but not dead, bacteria. Using bone marrow-derived macrophages from various TLRs and nucleotide-binding oligomerization domain-deficient mice, we further determined that IL-1ß production was dependent on TLR2 and TLR4, suggesting a participation of the leptospiral LPS to this process. Hypokaliemia in leptospirosis has been linked to the presence of glycolipoprotein, a cell wall component of L. interrogans that is known to inhibit the expression and functions of the Na/K-ATPase pump. We show in this study that glycolipoprotein activates the inflammasome and synergizes with leptospiral LPS to produce IL-1ß, mimicking the effect of whole bacteria. These results were confirmed in vivo, as wild-type mice expressed more IL-1ß in the kidney than TLR2/4-deficient mice 3 d postinfection with L. interrogans. Collectively, these findings provide the first characterization, to our knowledge, of bacteria-induced activation of the NLRP3 inflammasome through the downregulation of a specific host potassium transporter.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Proteínas de Transporte
/
ATPase Trocadora de Sódio-Potássio
/
Inflamassomos
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Leptospirose
/
Macrófagos
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
França