Antimicrobial Peptide Response to Blood Translocation of Bacterial DNA in Crohn's Disease Is Affected by NOD2/CARD15 Genotype
Antimicrobial Peptide Response to Blood Translocation of Bacterial DNA in Crohn's Disease Is Affected by NOD2/CARD15 Genotype
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DOI：
10.1002/ibd.21537
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发表时间：
2011-08-01
影响因子：
4.9
通讯作者：
Frances, Ruben
中科院分区：
文献类型：
--
作者：
Gutierrez, Ana;Holler, Ernst;Frances, Ruben
背景：克罗恩病（CD）患者中存在细菌DNA的血液易位。宿主的免疫细胞类型合作以抵抗细菌的侵害。一些抗菌肽在与细菌产物一起培养后是可诱导的，并且已经在它们与NOD 2/CARD 15之间建立了联系。目的是测试是否防御素和cathelicidin（LL-37）的表达和NOD 2/CARD 15基因突变的血液中性粒细胞相关的分子细菌易位事件CD patients.Methods：50例连续入院的CD患者和15名健康对照。考虑了患者的临床和分析特征。NOD 2/CARD 15基因分型、细菌DNA、防御素和cathelicidin基因的存在、中性粒细胞蛋白水平和血清细胞因子水平进行了研究。11人处于活动状态，9人处于缓解状态。对照组中不存在细菌DNA。在25例患者（50%）中发现了NOD 2/CARD 15突变，其中15例处于缓解期。60%的细菌DNA（+）和43%的细菌DNA（-）患者显示NOD 2/CARD 15突变。β-防御素2和LL-37 mRNA和蛋白水平在细菌DNA（+）患者中上调。β-防御素2和LL-37的表达仅在具有野生型NOD 2/CARD 15基因型的患者中与细菌DNA浓度相关。细菌DNA（-）患者的培养中性粒细胞证实了DEFB 2和LL-37与野生型NOD 2/CARD 15患者中细菌DNA浓度之间的胞壁酰二肽无关性。细菌DNA（+）患者的细胞因子水平升高，并与细菌DNA浓度相关。NOD 2/CARD 15基因型并没有影响这种correlations.Conclusions：β-防御素2，LL-37，和促炎细胞因子增加CD患者与细菌DNA的浓度依赖性的方式。NOD 2/CARD 15在调节这种反应中起关键作用。
Background: Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/CARD15. The aim was to test whether defensins and cathelicidin (LL-37) expression and NOD2/CARD15 mutations in blood neutrophils are related to molecular bacterial translocation events in CD patients.Methods: Fifty consecutively admitted CD patients and 15 healthy controls were included. Clinical and analytical characteristics of patients were considered. NOD2/CARD15 genotyping, presence of bacterial-DNA, defensin and cathelicidin gene, and protein levels in neutrophils and serum cytokine levels were studied.Results: Twenty patients (40%) presented bacterial-DNA in blood. Eleven were active and 9 were in remission. Bacterial-DNA was not present in controls. NOD2/CARD15 mutations were identified in 25 patients (50%), 15 of which were in remission. Sixty percent of bacterial-DNA(+) and 43% of bacterial-DNA(-) patients showed a NOD2/CARD15 mutation. beta-Defensin 2 and LL-37 mRNA and protein levels were upregulated in bacterial-DNA(+) patients. beta-Defensin 2 and LL-37 expression correlated with bacterial-DNA concentration only in patients with a wildtype NOD2/CARD15 genotype. Cultured neutrophils of bacterial-DNA(-) patients confirmed the muramyl dipeptide-independent association between DEFB2 and LL-37 with bacterial-DNA concentration in wildtype NOD2/CARD15 patients. Cytokine levels were increased in bacterial-DNA(+) patients and correlated with bacterial-DNA concentration. NOD2/CARD15 genotype did not influence this correlation.Conclusions: beta-Defensin 2, LL-37, and proinflammatory cytokines are increased in CD patients with bacterial-DNA in a concentration-dependent manner. NOD2/CARD15 plays a key role in the regulation of this response.