RESUMO
Prior exposure to lipopolysaccharides (LPS) induces a state of cell resistance to subsequent LPS restimulation, known as endotoxin tolerance, mainly by repressing the expression of pro-inflammatory cytokines. We established an endotoxin tolerance model in human monocytes Endotoxin-tolerant cells showed a decrease in IκBα degradation and diminished expression of Tumor necrosis factor (TNF) (both messenger RNA [mRNA] and protein content). The myeloid differentiation factor 88 (MyD88)/MyD88 splice variant (MyD88s) ratio, an indirect way to test the Toll-like receptor 4 (TLR4) MyD88-dependent signaling cascade, did not change in endotoxin-tolerant cells when compared to LPS-stimulated or -unstimulated ones. Remarkably, cell population analysis indicated a significant increase of the CD14+ CD16+ subset only under the endotoxin-tolerant condition. Furthermore, endotoxin-tolerant cells produced higher amounts of C-X-C motif chemokine 10 (CXCL10), a typical MyD88-independent cytokine.
Assuntos
Endotoxinas/imunologia , Tolerância Imunológica , Monócitos/imunologia , Quimiocina CXCL10/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/imunologia , Masculino , Monócitos/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fenótipo , Receptores de Superfície Celular/metabolismo , Receptores de IgG/metabolismo , Transdução de SinaisRESUMO
Patients with interleukin 12 (IL-12)p40 or IL-12 receptor ß1 (IL12Rß1) deficiencies are prone to develop infections caused by mycobacteria and salmonella; other infections have only been rarely observed. In this report we describe 2 unrelated patients with complete autosomal recessive IL12Rß1 deficiency who suffered from sepsis attributable to Klebsiella pneumoniae. A Mexican boy suffered from disseminated bacille Calmette-Guérin disease and infections caused by K pneumoniae and Candida albicans and had a fatal outcome. A Turkish girl living in France suffered from disseminated Nocardia nova infection and K pneumoniae sepsis. Therefore, Klebsiella infections should be considered in patients with IL12Rß1 deficiency. Conversely, IL12Rß1 deficiency should be considered in patients with unexplained klebsiellosis.