Cd1d-dependent regulation of bacterial colonization in the intestine of mice
Edward E.S. Nieuwenhuis, … , Andrew B. Onderdonk, Richard S. Blumberg
Edward E.S. Nieuwenhuis, … , Andrew B. Onderdonk, Richard S. Blumberg
Published April 6, 2009
Citation Information: J Clin Invest. 2009;119(5):1241-1250. https://doi.org/10.1172/JCI36509.
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Research Article Gastroenterology

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

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.

Authors

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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Figure 4

Enhanced intestinal colonization with E. coli of Cd1d–/– BALB/c mice within the entire intestine at t = 12 hours and within the jejunum at t = 120 hours and prevention of intestinal colonization with E. coli through Cd1d-restricted NKT cell activation.

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Enhanced intestinal colonization with E. coli of Cd1d–/– BALB/c mice wit...
(A) Germ-free Cd1d–/– BALB/c mice and WT BALB/c mice were orally inoculated with 50 CFUs per mouse of E. coli strain ATCC 25922. The viable number of bacteria were determined by culturing the luminal contents that were obtained from each part of the intestine at 12 hours after inoculation (data represent mean ± SEM; n = 6 for each group; *P < 0.05). (B) Germ-free Cd1d–/– mice (n = 4) and WT BALB/c mice (n = 5) were orally inoculated with 650 CFUs per mouse of E. coli strain ATCC 25922. The viable number of bacteria were determined by culturing the luminal contents that were obtained from each part of the intestine at t = 120 hours after inoculation (data represent mean ± SEM; n = 4 or 5 for each group; *P < 0.05). (C) Each germ-free WT mouse was treated intraperitoneally with 2 μg of αGalCer or PBS. Subsequently, mice were inoculated with 65 CFUs per mouse of E. coli strain ATCC 25922. At 24 hours after inoculation, the viable number of bacteria were determined by culturing the luminal contents that were obtained from each part of the intestine (data are mean ± SEM; probabilities were calculated by Student’s t tests; n = 6 for each group; *P < 0.05, **P < 0.005).