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Published on: December 16, 2021
Cd1d-dependent regulation of bacterial colonization in the intestine of mice
Edward E S Nieuwenhuis1, Tetsuya Matsumoto, Dicky Lindenbergh
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. e.nieuwenhuis@erasmusmc.nl
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 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.
Insights
Mice lacking the Cd1d molecule show increased intestinal bacterial colonization and translocation. Activating Cd1d-restricted T cells (NKT cells) reduces bacterial colonization, highlighting Cd1d
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Host mechanisms controlling intestinal commensal bacteria colonization are not well understood.
- Bacterial accumulation in the intestine impacts tissue homeostasis and immune pathologies.
Purpose of the Study:
- To investigate the role of Cd1d in regulating intestinal bacterial colonization.
- To elucidate host mechanisms controlling bacterial translocation and microbiota composition.
Main Methods:
- Comparison of bacterial colonization and translocation in Cd1d-deficient (Cd1d-/-) and wild-type (WT) mice under germ-free and specific pathogen-free conditions.
- Administration of common bacterial species (Pseudomonas aeruginosa, E. coli, Staphylococcus aureus, Lactobacillus gasseri).
- Activation of Cd1d-restricted T cells (NKT cells) using alpha-galactosylceramide.
- Analysis of intestinal microbiota composition and Paneth cell function in Cd1d-/- mice.
Main Results:
- Cd1d-/- mice exhibited increased intestinal colonization and bacterial translocation compared to WT mice.
- NKT cell activation significantly diminished intestinal bacterial colonization.
- Cd1d-/- mice showed altered microbiota composition with increased adherent bacteria.
- Germ-free Cd1d-/- mice displayed defects in Paneth cell granule ultrastructure and degranulation.
- In vitro studies demonstrated NKT cells induce lysozyme release from intestinal crypts.
Conclusions:
- Cd1d plays a crucial role in controlling intestinal bacterial colonization.
- Mechanisms involve the regulation of Paneth cell function and NKT cell activity.
- Cd1d-mediated immune responses are essential for maintaining intestinal homeostasis.
