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

Edward E S Nieuwenhuis, Tetsuya Matsumoto, Dicky Lindenbergh, Rob Willemsen, Arthur Kaser, Ytje Simons-Oosterhuis, Sylvia Brugman, Keizo Yamaguchi, Hiroki Ishikawa, Yuji Aiba, Yasuhiro Koga, Janneke N. Samsom, Kenshiro Oshima, Mami Kikuchi, Johanna C. Escher, Masahira Hattori, Andrew B. Onderdonk, Richard S. Blumberg

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119 Citations (Scopus)

Abstract

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 α- 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.

Original languageEnglish
Pages (from-to)1241-1250
Number of pages10
JournalJournal of Clinical Investigation
Volume119
Issue number5
DOIs
Publication statusPublished - 2009 May 1
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Nieuwenhuis, E. E. S., Matsumoto, T., Lindenbergh, D., Willemsen, R., Kaser, A., Simons-Oosterhuis, Y., Brugman, S., Yamaguchi, K., Ishikawa, H., Aiba, Y., Koga, Y., Samsom, J. N., Oshima, K., Kikuchi, M., Escher, J. C., Hattori, M., Onderdonk, A. B., & Blumberg, R. S. (2009). Cd1d-dependent regulation of bacterial colonization in the intestine of mice. Journal of Clinical Investigation, 119(5), 1241-1250. https://doi.org/10.1172/JCI36509