Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14.

Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14.
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DOI:
10.1084/jem.191.10.1807
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发表时间:
2000-05-15
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Schiffrin EJ
Schiffrin EJ
中科院分区:
其他
文献类型:
--
作者:
Labéta MO;Vidal K;Nores JE;Arias M;Vita N;Morgan BP;Guillemot JC;Loyaux D;Ferrara P;Schmid D;Affolter M;Borysiewicz LK;Donnet-Hughes A;Schiffrin EJ

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在迄今为止无菌的胎儿肠道中,人们对出生后对细菌的先天免疫知之甚少。长期以来,母乳喂养与胃肠道感染、炎症和过敏性疾病的发病率较低有关。我们在人类母乳中发现了一种48 kD的多肽,我们通过质谱和测序证实它是细菌模式识别受体CD 14(sCD 14)的可溶性形式。乳汁sCD 14(m-sCD 14)浓度比非妊娠、妊娠或哺乳期妇女血清sCD 14浓度高20倍。与此相反,脂多糖(LPS)结合蛋白是在非常低的水平。乳腺上皮细胞产生48 kD sCD 14。m-sCD 14介导LPS和整个细菌对CD 14阴性细胞(包括肠上皮细胞)的活化,导致先天性免疫应答分子的释放。m-sCD 14在婴儿配方奶粉和市售牛奶中检测不到,尽管它存在于牛初乳中。这些研究结果表明,sCD 14在肠道细菌定植期间在母乳中的哨兵作用,并表明m-sCD 14可能参与调节局部先天性和适应性免疫应答,从而控制新生儿肠道的稳态。
Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum sCD14 from nonpregnant, pregnant, or lactating women. In contrast, lipopolysaccharide (LPS)-binding protein was at very low levels. Mammary epithelial cells produced 48-kD sCD14. m-sCD14 mediated activation by LPS and whole bacteria of CD14 negative cells, including intestinal epithelial cells, resulting in release of innate immune response molecules. m-sCD14 was undetectable in the infant formulas and commercial (cows') milk tested, although it was present in bovine colostrum. These findings indicate a sentinel role for sCD14 in human milk during bacterial colonization of the gut, and suggest that m-sCD14 may be involved in modulating local innate and adaptive immune responses, thus controlling homeostasis in the neonatal intestine.
膜攻击复合物抑制性蛋白CD59在人类精液血浆中的生理相关性:CD59存在于细胞外细胞器(前列腺素)上,结合细胞膜,并抑制补体介导的裂解。
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