Lactobacilli and streptococci activate NF-κB and STAT signaling pathways in human macrophages

被引:160
作者
Miettinen, M [1 ]
Lehtonen, A [1 ]
Julkunen, I [1 ]
Matikainen, S [1 ]
机构
[1] Natl Publ Hlth Inst, Dept Virol, SF-00300 Helsinki, Finland
关键词
D O I
10.4049/jimmunol.164.7.3733
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Gram-positive bacteria induce the production of several cytokines in human leukocytes, The molecular mechanisms involved in Gram-positive bacteria-induced cytokine production have been poorly characterized. In this work we demonstrate that both nonpathogenic Lactobacillus rhamnosus GG and pathogenic Streptococcus pyogenes (group A streptococci) induce NF-kappa B and STAT DNA-binding activity in human primary macrophages as analyzed by EMSA, NF-kappa B activation was rapid and was not inhibited by a protein synthesis inhibitor cycloheximide, suggesting that these bacteria could directly activate NF-kappa B. STAT1, STAT3, and IFN regulatory factor-1 DNA binding was induced by both bacteria with delayed kinetics compared with NF-kappa B. In addition, streptococci induced the formation of IFN-alpha-specific transcription factor complex and IFN-stimulated gene factor-3 (ISGF3), STAT1 and STAT3 activation and ISGF3 complex formation were inhibited by cycloheximide or by neutralization with IFN-alpha/beta-specific Abs, Streptococci were more potent than lactobacilli in inducing STAT1, ISGF3, and IFN regulatory factor-1 DNA binding. Accordingly, only streptococci induced IFN-alpha production, The activation of the IFN-alpha signaling pathway by streptococci could play a role in the pathogenesis of these bacteria, These results indicate that extracellular Gram-positive bacteria activate transcription factors involved in cytokine signaling by two mechanisms: directly, leading to NF-kappa B activation, and indirectly via cytokines, leading to STAT activation.
引用
收藏
页码:3733 / 3740
页数:8
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