title: SR-A, MARCO and TLRs differentially recognise selected surface proteins from Neisseria meningitidis: an example of fine specificity in microbial ligand recognition by innate immune receptors.
abstract: Macrophages express various classes of pattern recognition receptors involved in innate immune recognition of artificial, microbial and host-derived ligands. These include the scavenger receptors (SRs), which are important for phagocytosis, and the Toll-like receptors (TLRs) involved in microbe sensing. The class A macrophage scavenger receptor (SR-A) and macrophage receptor with a collagenous structure (MARCO) display similar domain structures and ligand-binding specificity, which has led to the assumption that these two receptors may be functionally redundant. In this study we show that SR-A and MARCO differentially recognise artificial polyanionic ligands as well as surface proteins from the pathogenic bacterium Neisseria meningitidis. We show that, while acetylated low-density lipoprotein (AcLDL) is a strong ligand for SR-A, it is not a ligand for MARCO. Of the neisserial proteins that were SR ligands, some were ligands for both receptors, while other proteins were only recognised by either SR-A or MARCO. We also analysed the potential of these ligands to act as TLR agonists and assessed the requirement for SR-A and MARCO in pro-inflammatory cytokine induction. SR ligation alone did not induce cytokine production; however, for proteins that were both SR and TLR ligands, the SRs were required for full activation of TLR pathways.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, UK.
authors.forename: Annette
authors.initials: A
authors.lastname: Plüddemann
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: Marko
authors.initials: M
authors.lastname: Sankala
authors.forename: Silvana
authors.initials: S
authors.lastname: Savino
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D007113:Immunity, Innate; D008024:Ligands; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008589:Meningococcal Infections / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008024:Ligands; C092228:Marco protein, mouse; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D051193:Toll-Like Receptors