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Peptidoglycan recognition protein–peptidoglycan complexes increase monocyte/macrophage activation and enhance the inflammatory response
Author(s) -
De Marzi Mauricio C.,
Todone Marcos,
Ganem María B.,
Wang Qian,
Mariuzza Roy A.,
Fernández Marisa M.,
Malchiodi Emilio L.
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12460
Subject(s) - peptidoglycan , pattern recognition receptor , biology , monocyte , lipopolysaccharide , microbiology and biotechnology , biochemistry , chemistry , immunology , innate immune system , receptor , cell wall
Summary Peptidoglycan 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 ‐I α and PGRP ‐I β . Mammalian PGRP ‐S has been implicated in intracellular destruction of bacteria by polymorphonuclear cells, PGRP ‐I α and PGRP ‐I β 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 ‐I α 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 ‐I α cause slight damage in the bacterial membrane. Monocytes/macrophages increase Staphylococcus aureus phagocytosis in the presence of PGRP ‐S, PGRP ‐I α and PGRP ‐I β . 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 CD 14, CD 80 and CD 86, and enhance secretion of interleukin‐8, interleukin‐12 and tumour necrosis factor‐ α , but reduce interleukin‐10, clearly inducing an inflammatory profile.