Control of intestinal Nod2-mediated peptidoglycan recognition by epithelium-associated lymphocytes. Mucosal Immunol 2011 May;4(3):325-34
Date
10/29/2010Pubmed ID
20980996DOI
10.1038/mi.2010.71Scopus ID
2-s2.0-79955079700 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
Innate immune recognition of the bacterial cell wall constituent peptidoglycan by the cytosolic nucleotide-binding oligomerization domain 2 (Nod2) receptor has a pivotal role in the maintenance of intestinal mucosal homeostasis. Whereas peptidoglycan cleavage by gut-derived lysozyme preserves the recognition motif, the N-acetylmuramoyl-L-alanine amidase activity of the peptidoglycan recognition protein 2 (PGLYRP-2) destroys the Nod2-detected muramyl dipeptide structure. PGLYRP-2 green fluorescent protein (GFP) reporter and wild-type mice were studied by flow cytometry and quantitative RT-PCR to identify Pglyrp-2 expression in cells of the intestinal mucosa and reveal a potential regulatory function on epithelial peptidoglycan recognition. CD3(+)/CD11c(+) T lymphocytes revealed significant Pglyrp-2 expression, whereas epithelial cells and intestinal myeloid cells were negative. The mucosal Pglyrp-2-expressing lymphocyte population demonstrated a mixed T-cell receptor (TCR) αβ or γδ phenotype with predominant CD8α and less so CD8β expression, as well as significant staining for the activation markers B220 and CD69, presenting a typical intraepithelial lymphocyte phenotype. Importantly, exposure of peptidoglycan to PGLYRP-2 significantly reduced Nod2/Rip2-mediated epithelial activation. Also, moderate but significant alterations of the intestinal microbiota composition were noted in Pglyrp-2-deficient animals. PGLYRP-2 might thus have a significant role in regulation of the enteric host-microbe homeostasis.
Author List
Duerr CU, Salzman NH, Dupont A, Szabo A, Normark BH, Normark S, Locksley RM, Mellroth P, Hornef MWAuthors
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of WisconsinAniko Szabo PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntigens, CD
Cells, Cultured
Genetic Engineering
Green Fluorescent Proteins
Host-Pathogen Interactions
Intestinal Mucosa
Lymphocyte Activation
Metagenome
Mice
Mice, Inbred C57BL
Mice, Knockout
N-Acetylmuramoyl-L-alanine Amidase
Nod2 Signaling Adaptor Protein
Peptidoglycan
Proteins
Receptors, Antigen, T-Cell
T-Lymphocytes