Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis.
Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis.
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作者：
Luther J;Owyang SY;Takeuchi T;Cole TS;Zhang M;Liu M;Erb-Downward J;Rubenstein JH;Chen CC;Pierzchala AV;Paul JA;Kao JY
最近出现的流行病学数据表明，幽门螺杆菌(H.Pylori)可以预防某些慢性炎症性疾病，如炎症性肠病(IBD)。然而，观察到的幽门螺杆菌和IBD之间的反向关联的机制尚未描述。利用MacVector软件计算不同细菌基因组中免疫刺激(ISS)序列的免疫调节(IRS)频率。通过细胞因子的产生分析DNA冲击的小鼠骨髓来源的树突状细胞(BMDC)和人浆细胞样树突状细胞(PDC)诱导的I型干扰素和IL-12应答。检测幽门螺杆菌DNA对大肠杆菌产生I型干扰素和IL-12的影响。在DSS结肠炎模型中评估了幽门螺杆菌DNA抑制的体内意义。对幽门螺杆菌定植和非定植患者的系统I型干扰素水平进行了评估。我们发现，幽门螺杆菌DNA的IRS：ISS比率显著升高。体外实验表明，幽门螺杆菌DNA不能刺激小鼠BMDCs或人pDC产生I型干扰素或IL-12。此外，幽门螺杆菌DNA能够抑制大肠杆菌产生I型干扰素和IL-12。在急性和慢性模型中，与大肠杆菌DNA或赋形剂对照相比，在诱导DSS结肠炎之前注射H.Pylori DNA显著改善了结肠炎的严重程度。最后，发现幽门螺杆菌定植的患者的系统I型干扰素水平低于未定植的对照组。总体而言，我们的研究表明，幽门螺杆菌DNA具有下调DC的促炎反应的能力，这可能部分解释了幽门螺杆菌与IBD之间的反向关联。
Recently there has been emerging epidemiological data to suggest Helicobacter pylori (H. pylori) may protect against certain chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, the mechanism for the observed inverse association between H. pylori and IBD has not been described. The frequency of immunoregulatory (IRS) to immunostimulatory (ISS) sequences within the genome of various bacteria was calculated using MacVector software. The induction of type I IFN and IL-12 responses by DNA-pulsed murine bone marrow–derived dendritic cells (BMDC) and human plasmacytoid dendritic cells (pDC) was analyzed by cytokine production. The effect of H. pylori DNA on E. coli DNA production of type I IFN and IL-12 was assessed. The in vivo significance of H. pylori DNA suppression was assessed in a DSS-model of colitis. The systemic levels of type I IFN were assessed in H. pylori-colonized and non-colonized patients. We showed that H. pylori DNA has a significantly elevated IRS:ISS ratio. In vitro experiments revealed the inability of H. pylori DNA to stimulate type I IFN or IL-12 production from mouse BMDCs or human pDCs. Additionally, H. pylori DNA was able to suppress E. coli-DNA production of type I IFN and IL-12. Administration of H. pylori DNA prior to the induction of DSS colitis significantly ameliorated the severity of colitis as compared to E. coli DNA or vehicle control in both an acute and chronic model. Finally, the systemic levels of type I IFN were found to be lower in H. pylori-colonized patients versus non-colonized controls. Overall, our study indicates that H pylori DNA has the ability to down-regulate pro-inflammatory responses from DCs and this may in part explain the inverse association between H. pylori and IBD.
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DOI：
10.1086/590158
发表时间：
2008-08-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Chen Y;Blaser MJ
通讯作者：
Blaser MJ
影响因子：
3.4
作者：
Keenan, J. I.;Beaugie, C. R.;Frizelle, F. A.
通讯作者：
Frizelle, F. A.
DOI：
10.1073/pnas.0708469104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Abe, Kazumichi;Nguyen, Kim Phung;Raz, Eyal
通讯作者：
Raz, Eyal
影响因子：
6.7
作者：
Dorer MS;Talarico S;Salama NR
通讯作者：
Salama NR
DOI：
10.1084/jem.20090213
发表时间：
2009-08-31
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huys L;Van Hauwermeiren F;Dejager L;Dejonckheere E;Lienenklaus S;Weiss S;Leclercq G;Libert C
通讯作者：
Libert C