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) αß or γδ phenotype with predominant CD8α and less so CD8ß 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.
Subject(s)
Intestinal Mucosa/metabolism , N-Acetylmuramoyl-L-alanine Amidase/metabolism , Nod2 Signaling Adaptor Protein/metabolism , Proteins/metabolism , T-Lymphocytes/metabolism , Animals , Antigens, CD/metabolism , Cells, Cultured , Genetic Engineering , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Host-Pathogen Interactions , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Lymphocyte Activation , Metagenome , Mice , Mice, Inbred C57BL , Mice, Knockout , Nod2 Signaling Adaptor Protein/genetics , Nod2 Signaling Adaptor Protein/immunology , Peptidoglycan/immunology , Proteins/genetics , Proteins/immunology , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/pathologySubject(s)
Antigens, CD , Bacteria/immunology , Bacterial Infections/immunology , Neutrophils/immunology , ADP-ribosyl Cyclase , ADP-ribosyl Cyclase 1 , Antigens, Differentiation/metabolism , Calcium Signaling , Chemotaxis, Leukocyte , Humans , Lung/immunology , Membrane Glycoproteins , NAD+ Nucleosidase/metabolism , Neutrophils/metabolism , Pneumonia, Pneumococcal/immunologyABSTRACT
During the last 10 y we have observed an increased incidence of pneumococcal bacteremia in Sweden. In order to study the serotype distribution over time we collected 1136 invasive pneumococcal isolates from 1987, 1992 and 1997 from Swedish microbiological laboratories. Currently, new pneumococcal conjugate vaccines are being considered for introduction in the general childhood vaccination program in several countries, including Sweden. We studied the potential vaccine coverage rate for the new conjugate vaccines among our Swedish invasive isolates. We found that the serotype distribution fluctuated with time and observed a surprisingly low potential coverage rate for the 7-valent vaccine in Sweden, in contrast to other countries. Therefore we argue that pneumococcal conjugate vaccines have to be tailored to suit current, local serotype patterns and most likely will need to be changed over time.
