Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract.
The gene encoding the Nod2 protein is frequently mutated in Crohn's disease (CD) patients, although the physiological function of Nod2 in the intestine remains elusive. Here we show that protective immunity mediated by Nod2 recognition of bacterial muramyl dipeptide is abolished in Nod2-deficient mice. These animals are susceptible to bacterial infection via the oral route but not through intravenous or peritoneal delivery. Nod2 is required for the expression of a subgroup of intestinal anti-microbial peptides, known as cryptdins. The Nod2 protein is thus a critical regulator of bacterial immunity within the intestine, providing a possible mechanism for Nod2 mutations in CD.
Kobayashi
Koichi S
KS
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Chamaillard
Mathias
M
Ogura
Yasunori
Y
Henegariu
Octavian
O
Inohara
Naohiro
N
Nuñez
Gabriel
G
Flavell
Richard A
RA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D007082:Ileum / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D007410:Intestinal Diseases / Q000276:immunology / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000633:toxicity; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein; D020411:Oligonucleotide Array Sequence Analysis; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology; D012709:Serum Albumin / Q000276:immunology; D015398:Signal Transduction; D013154:Spleen / Q000382:microbiology; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D023084:alpha-Defensins / Q000096:biosynthesis* / Q000235:genetics
D007136:Immunoglobulins; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D012709:Serum Albumin; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D023084:alpha-Defensins; C059569:cryptdin; D000119:Acetylmuramyl-Alanyl-Isoglutamine