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Control of intestinal Nod2-mediated peptidoglycan recognition by epithelium-associated lymphocytes. Mucosal Immunol 2011 May;4(3):325-34 PMID: 20980996

Pubmed ID

20980996

Abstract

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 MW

Authors

Nita H. Salzman MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
Aniko Szabo PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin




Scopus

2-s2.0-79955079700   18 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Antigens, 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
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6