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首页> 外文学位 >Modulating innate and adaptive immunity in the Toxoplasma gondii-induced model of inflammatory bowel disease.
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Modulating innate and adaptive immunity in the Toxoplasma gondii-induced model of inflammatory bowel disease.

机译：在弓形虫诱导的炎症性肠病模型中调节先天性和适应性免疫。

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摘要

Inbred C57BL/6 mice develop an acute necrotizing ileitis following oral infection with Toxoplasma gondii that is associated with massive inflammatory infiltrates and morphologic tissue changes consistent with human Crohn's disease. In the course of the infection, the parasite interacts with both the innate and adaptive arms of the immune system. TLR9-dependant mechanisms, triggered by the parasite, induce Crp release in the lumen. Our results indicate that T. gondii induces Crp-3/-5 production and release by PCs via a TLR9-dependant production of type I IFN. Cryptdins have a limited direct effect against the parasite, but may affect the early control of T. gondii invasiveness by promoting the initiation of a protective Th1 response against the parasite. We also examined the ability of CD4+CD25+FoxP3+ T regulatory cells (Treg) to control T. gondii-induced ileitis. To determine whether the Treg cells generated during infection were suppressive, we adoptively transferred Treg from naive or T. gondii infected mice to naive animals, which were in turn infected. Mice that received T reg from infected mice showed reduced morbidity and improved small intestine pathology. Our results demonstrate that pathogen-experienced Treg are superior to naive Treg in control of T. gondii --induced ileitis. Finally, we investigated leukocyte cell trafficking to the intestine and CNS. Treatment with an analogue inhibitor of sphingosine-1-phosphate (S1P) reduced clinical and inflammatory changes in the small intestine. The brain parasite burden of treated mice was reduced indicating that S1P is required for both lymphocyte and parasite trafficking to the intestine and CNS following oral infection by T. gondii. Taken together, the studies presented herein demonstrate several potential targets for the treatment of inflammatory bowel disease.
机译：自交C57BL / 6小鼠在被弓形虫口腔感染后发展为急性坏死性回肠炎，这与大量炎性浸润和与人类克罗恩病一致的形态学组织改变有关。在感染过程中，寄生虫与免疫系统的固有臂和适应臂都相互作用。由寄生虫触发的TLR9依赖性机制诱导内腔中Crp释放。我们的结果表明，刚地弓形虫诱导PCs通过TLR9依赖性I型干扰素产生Crp-3 / -5和释放。 Cryptdins对寄生虫的直接作用有限，但可能通过促进针对寄生虫的保护性Th1反应的启动而影响刚地弓形虫侵袭的早期控制。我们还检查了CD4 + CD25 + FoxP3 + T调节细胞（Treg）控制弓形虫诱导的回肠炎的能力。为了确定感染过程中产生的Treg细胞是否具有抑制作用，我们将Treg从幼稚或刚地弓形虫感染的小鼠过继转移到幼稚动物中，然后再将其感染。从感染小鼠接受T reg的小鼠显示出降低的发病率并改善了小肠病理。我们的结果表明，在控制弓形虫诱发的回肠炎方面，经验丰富的病原体Treg优于天然Treg。最后，我们调查了白细胞向肠道和中枢神经系统的运输。用鞘氨醇-1-磷酸（S1P）类似物抑制剂治疗可减少小肠的临床和炎症变化。经治疗的小鼠的脑部寄生虫负担降低，表明在刚地弓形虫口服感染后，淋巴细胞和寄生虫向肠道和中枢神经系统的运输都需要S1P。综上所述，本文提出的研究证明了治疗炎性肠病的几种潜在靶标。

著录项

  • 作者

    Mielcarz, Daniel William.;

  • 作者单位

    Dartmouth College.;

  • 授予单位 Dartmouth College.;
  • 学科 Biology Microbiology.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 217 p.
  • 总页数 217
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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