Cd1d-dependent regulation of bacterial colonization in the intestine of mice

被引：144

作者：

Nieuwenhuis, Edward E. S. ^{[1
,2
]}

Matsumoto, Tetsuya ^{[2
,3
]}

Lindenbergh, Dicky ^{[1
]}

Willemsen, Rob ^{[4
]}

Kaser, Arthur ^{[2
]}

Simons-Oosterhuis, Ytje ^{[1
]}

Brugman, Sylvia ^{[1
]}

Yamaguchi, Keizo ^{[5
]}

Ishikawa, Hiroki ^{[6
]}

Aiba, Yuji ^{[6
]}

Koga, Yasuhiro ^{[6
]}

Samsom, Janneke N. ^{[1
]}

Oshima, Kenshiro ^{[7
]}

Kikuchi, Mami ^{[7
,8
]}

Escher, Johanna C. ^{[1
]}

Hattori, Masahira ^{[7
]}

Onderdonk, Andrew B. ^{[9
]}

Blumberg, Richard S. ^{[2
]}

机构：

[1] Erasmus MC, Pediat Lab, Rotterdam, Netherlands

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Gastroenterol Div,Dept Med, Boston, MA 02115 USA

[3] Tokyo Med & Dent Univ, Dept Microbiol, Tokyo, Japan

[4] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[5] Toho Univ, Sch Med, Dept Microbiol, Tokyo, Japan

[6] Tokai Univ, Sch Med, Dept Infect Dis, Kanagawa 2591100, Japan

[7] Univ Tokyo, Grad Sch Frontier Sci, Kashiwa, Chiba, Japan

[8] Kureha Corp, Biomed Res Labs, Shinjuku Ku, Tokyo, Japan

[9] Harvard Univ, Sch Med, Channing Lab, Dept Pathol, Boston, MA 02115 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2009年 / 119卷 / 05期

基金：

日本学术振兴会;

关键词：

KILLER T-CELLS; GENOME-WIDE ASSOCIATION; PANETH CELLS; ULCERATIVE-COLITIS; ALPHA-DEFENSINS; ANTIGEN PRESENTATION; IMMUNE HOMEOSTASIS; COMMENSAL BACTERIA; EPITHELIAL-CELLS; CROHNS-DISEASE;

D O I：

10.1172/JCI36509

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The accumulation of certain species of bacteria in the intestine is involved in both tissue homeostasis and immune-mediated pathologies. The host mechanisms involved in controlling intestinal colonization with commensal bacteria are poorly understood. We observed that under specific pathogen-free or germ-free conditions, intragastric administration of Pseudomonas aeruginosa, E. coli, Staphylococcus aureus, or Lactobacillus gasseri resulted in increased colonization of the small intestine and bacterial translocation in mice lacking Cd1d, an MHC class I-like molecule, compared with WT mice. In contrast, activation of Cd1d-restricted T cells (NKT cells) with alpha-galactosylceramide caused diminished intestinal colonization with the same bacterial strains. We also found prominent differences in the composition of intestinal microbiota, including increased adherent bacteria, in Cd1d(-/-) mice in comparison to WT mice under specific pathogen-free conditions. Germ-free Cd1d(-/-) mice exhibited a defect in Paneth cell granule ultrastructure and ability to degranulate after bacterial colonization. In vitro, NKT cells were shown to induce the release of lysozyme from intestinal crypts. Together, these data support a role for Cd1d in regulating intestinal colonization through mechanisms that include the control of Paneth cell function.

引用

页码：1241 / 1250

页数：10

共 54 条

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