Peptidoglycan recognition protein–peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response

Abstract

SummaryPeptidoglycan recognition proteins (PGRP) are pattern recognition receptors that can bind or hydrolyse peptidoglycan (PGN). Four human PGRP have been described: PGRP-S, PGRP-L, PGRP-Ia and PGRP-Ib. Mammalian PGRP-S has been implicated in intracellular destruction of bacteria by polymorphonuclear cells, PGRP-Ia and PGRP-Ib have been found in keratinocytes and epithelial cells, and PGRP-L is a serum protein that hydrolyses PGN. We have expressed recombinant human PGRP and observed that PGRP-S and PGRP-Ia exist as monomer and disulphide dimer proteins. The PGRP dimers maintain their biological functions. We detected the PGRP-S dimer in human serum and polymorphonuclear cells, from where it is secreted after degranulation; these cells being a possible source of serum PGRP-S. Recombinant PGRP do not act as bactericidal or bacteriostatic agents in the assayed conditions; however, PGRP-S and PGRP-Ia cause slight damage in the bacterial membrane. Monocytes/ macrophages increase Staphylococcus aureus phagocytosis in the presence of PGRP-S, PGRP-Ia and PGRP-Ib. All PGRP bind to monocyte/macrophage membranes and are endocytosed by them. In addition, all PGRP protect cells from PGN-induced apoptosis. PGRP increase THP-1 cell proliferation and enhance activation by PGN. PGRP-S-PGN complexes increase the membrane expression of CD14, CD80 and CD86, and enhance secretion of interleukin-8, interleukin-12 and tumour necrosis factor-a, but reduce interleukin-10, clearly inducing an inflammatory profile.

Licochalcone E protects against carbon tetrachloride-induced liver toxicity by activating peroxisome proliferator-activated receptor gamma

“…Inflammation, which plays an important role in many disease states, is associated with enhanced expression of adhesive molecules in the vasculature, resulting in the infiltration of larger populations of neutrophils and monocytes/macrophages ( 20 ). The release of proinflammatory cytokines from these activated leukocytes can then in turn cause tissue damage ( 21 ).…”

Peripheral Blood Leukocytes Interleukin-1 Beta (IL-1β) Cytokine Hyper-Reactivity in Chronic Periodontitis

“…Peptidoglycan is also a common component of the cell wall in periopathogens. Peptidoglycan recognition in the protein-peptidoglycan complexes increases monocyte/macrophage activation and enhances the inflammatory response [25]. …”

Peptidoglycan Recognition Protein 3 Does Not Alter the Outcome of Pneumococcal Pneumonia in Mice

“…More recent research indicates that mammalian PGLYRPs may also have immunomodulatory functions which are independent of their bactericidal or enzymatic properties ( Dziarski and Gupta, 2010 ). These immune modulatory functions were suggested to be even more important than direct antibacterial effects of these proteins, because (i) the direct antimicrobial functions are often inhibited by physiological concentrations of, e.g., salt and proteins, (ii) the relatively high dosage needed for antimicrobial activity is often not reached in the in vivo situation and (iii) immune modulation and antimicrobial functions can be mediated via independent mechanisms as seen for PGLYRPs where non-bactericidal immune modulatory PGLYRPs were expressed by E. coli ( De Marzi et al, 2015 ; Dukhanina et al, 2015 ; Hancock et al, 2016 ). For example, PGLYRP3 enhances phagocytosis and the pro-inflammatory response to peptidoglycan (PGN) in THP-1 cells ( De Marzi et al, 2015 ).…”