Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid.
Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid.
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DOI：
10.1186/1476-9255-9-7
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发表时间：
2012-03-16
期刊：
影响因子：
--
通讯作者：
Mohamadzadeh M
中科院分区：
文献类型：
--
作者：
Zadeh M;Khan MW;Goh YJ;Selle K;Owen JL;Klaenhammer T;Mohamadzadeh M
炎症性肠病的细胞和分子机制尚未完全了解;然而，数据表明，由细菌基因产物（包括脂磷壁酸（LTA））诱导的不受控制的慢性炎症可能引发结肠炎症，导致疾病发病机制。LTA是革兰氏阳性菌的组成糖脂，与脂多糖具有许多炎症特性，并通过Toll样受体2在严重炎症反应的发病机制中起关键作用。因此，我们阐明了LTA在体内免疫刺激和诱导结肠炎中的作用。为了更好地理解肠道微生物群及其基因产物用于诱导或破坏炎症的分子机制，特别是改变的表面层蛋白表达对LTA介导的促炎反应的影响，缺失编码SlpB和SlpX的嗜酸乳杆菌表面层蛋白（Slp）基因，产生继续表达SlpA的SlpB-和SlpX-突变体（编号为NCK 2031）。我们的数据显示NCK 2031、野生型L.嗜酸乳杆菌（NCK 56）和纯化的金黄色葡萄球菌-LTA。与LTA缺陷型菌株NCK 2025相反，LTA表达型菌株NCK 2031和NCK 56以及S. aureus-LTA在体内诱导促炎性先天性和T细胞免疫应答。此外，NCK 2031和S.补充在饮用水中的aureus-LTA保护小鼠免受DSS-结肠炎，但相反，诱导了显著的肠道炎症，导致严重的结肠炎和组织破坏。这些结果表明，直接改变两个L。嗜酸乳杆菌NCFM-Slps没有改善LTA诱导的促炎信号和随后的结肠炎。
The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA), may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s) of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp) genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031). Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56), and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction. These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.
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DOI：
10.1126/science.1195568
发表时间：
2010-12-24
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Lee YK;Mazmanian SK
通讯作者：
Mazmanian SK
DOI：
10.1084/jem.188.2.305
发表时间：
1998-07-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kengatharan KM;De Kimpe S;Robson C;Foster SJ;Thiemermann C
通讯作者：
Thiemermann C
影响因子：
3.1
作者：
Kullberg, MC;Rothfuchs, AG;Sher, A
通讯作者：
Sher, A
影响因子：
4.4
作者：
Brimnes, J;Allez, M;Mayer, L
通讯作者：
Mayer, L
影响因子：
4.4
作者：
Kaji, Rumi;Kiyoshima-Shibata, Junko;Shida, Kan
通讯作者：
Shida, Kan