Roles of bacterial flora in endotoxin shock mediated vi*

细菌菌群在内毒素休克介导的 vi* 中的作用

• 批准号: 6986213
• 负责人: KOICHI S KOBAYASHI
• 金额: $ 3.94万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-03 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986213
• 关键词: Czech Republic; biological signal transduction; cell wall; endotoxins; enteric bacteria; enzyme linked immunosorbent assay; genetically modified animals; gram negative bacteria; laboratory mouse; lipopolysaccharides; polymerase chain reaction; septic shock; tissue /cell culture; toll like receptor

DESCRIPTION (provided by applicant) Approximately 20000 people die from septic shock every year alone in this country as an outcome of gram negative bacterial infection. Lipopolysaccharide (LPS) or endotoxin, a structural component of outer cell wall, is a major effector and can activate the innate immune system via Toll-like receptors (TLRs) and lead to multiple organ damage, termed endotoxin shock. Human bodies are cohabitating with commensal bacterial flora. The largest observed is the one in the intestinal tract which is approximately 1 kg of bacteria/adult of weight. These bacterial flora continuously yield large amounts of bacterial products such as LPS. It has been shown that previous exposure to bacterial products change the sensitivity to LPS challenge in vitro and in vivo. Since LPS produced by commensal bacterial flora in the intestine is actually observed in blood circulation in the portal vein in laboratory animals, it is conceivable that commensal bacterial flora simulate the immune system, leading to the change of sensitivity to endotoxin shock via TLRs. We will test if commensal bacterial flora alter TLR signaling and sensitivity to endotoxin shock in vivo, using mutant strains of mice with increased TLR signaling and decreased TLR signaling. This research is performed primarily in the Institute of Microbiology AS CR in the Czech Republic in collaboration with Helena Tlaskalova as an extension of NIH grant # P01 AI36529.

描述（由申请人提供） 在这个国家，每年大约有20000人死于败血性休克，这是革兰氏阴性细菌感染的结果。内毒素（LPS）是细胞外壁的结构成分，是一种主要的效应因子，可通过Toll样受体（TLR）激活先天性免疫系统，导致多器官损伤，称为内毒素休克。 人体与肠道细菌植物群共存。观察到的最大细菌是肠道中的细菌，约为1 kg细菌/成人体重。这些细菌植物群连续产生大量的细菌产物如LPS。已经表明，先前暴露于细菌产物改变了体外和体内对LPS攻击的敏感性。由于在实验动物门静脉的血液循环中实际观察到肠内肠道细菌植物群产生的LPS，因此可以想象肠道细菌植物群模拟免疫系统，导致通过TLR对内毒素休克的敏感性改变。我们将使用TLR信号增加和TLR信号减少的小鼠突变株来测试体内细菌植物群是否改变TLR信号和对内毒素休克的敏感性。本研究主要在捷克共和国AS CR微生物学研究所与Helena Tlaskalova合作进行，作为NIH资助# P01 AI 36529的扩展。

项目成果

Altered gut microbiota promotes colitis-associated cancer in IL-1 receptor-associated kinase M-deficient mice.

• DOI: 10.1097/mib.0b013e318281330a
• 发表时间: 2013-05
• 期刊: Inflammatory bowel diseases
• 影响因子: 4.9
• 作者: Klimesova K;Kverka M;Zakostelska Z;Hudcovic T;Hrncir T;Stepankova R;Rossmann P;Ridl J;Kostovcik M;Mrazek J;Kopecny J;Kobayashi KS;Tlaskalova-Hogenova H
• 通讯作者: Tlaskalova-Hogenova H

Negative regulation of Toll-like receptor signaling plays an essential role in homeostasis of the intestine.

• DOI: 10.1002/eji.201040479
• 发表时间: 2011-01
• 期刊: EUROPEAN JOURNAL OF IMMUNOLOGY
• 影响因子: 5.4
• 作者: Biswas, Amlan;Wilmanski, Jeanette;Forsman, Huamei;Hrncir, Tomas;Hao, Liming;Tlaskalova-Hogenova, Helena;Kobayashi, Koichi S.
• 通讯作者: Kobayashi, Koichi S.

Gut microbiota and lipopolysaccharide content of the diet influence development of regulatory T cells: studies in germ-free mice.

• DOI: 10.1186/1471-2172-9-65
• 发表时间: 2008-11-06
• 期刊: BMC immunology
• 影响因子: 3
• 作者: Hrncir T;Stepankova R;Kozakova H;Hudcovic T;Tlaskalova-Hogenova H
• 通讯作者: Tlaskalova-Hogenova H