Cd1d-dependent regulation of bacterial colonization in the intestine of mice.
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.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. e.nieuwenhuis@erasmusmc.nl
Edward E S
EE
Nieuwenhuis
Tetsuya
T
Matsumoto
Dicky
D
Lindenbergh
Rob
R
Willemsen
Arthur
A
Kaser
Ytje
Y
Simons-Oosterhuis
Sylvia
S
Brugman
Keizo
K
Yamaguchi
Hiroki
H
Ishikawa
Yuji
Y
Aiba
Yasuhiro
Y
Koga
Janneke N
JN
Samsom
Kenshiro
K
Oshima
Mami
M
Kikuchi
Johanna C
JC
Escher
Masahira
M
Hattori
Andrew B
AB
Onderdonk
Richard S
RS
Blumberg
D000818:Animals; D055610:Antigens, CD1d / Q000502:physiology*; D001419:Bacteria / Q000276:immunology*; D015550:Cell Degranulation / Q000502:physiology; D004926:Escherichia coli / Q000276:immunology; D005243:Feces / Q000382:microbiology; D005699:Galactosylceramides / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D007778:Lactobacillus / Q000276:immunology; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology; D019879:Paneth Cells / Q000502:physiology / Q000648:ultrastructure; D011550:Pseudomonas aeruginosa / Q000276:immunology; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D022142:Secretory Vesicles / Q000737:chemistry / Q000648:ultrastructure; D013047:Specific Pathogen-Free Organisms / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D005699:Galactosylceramides; D012336:RNA, Ribosomal, 16S; C493154:alpha-galactosylceramide