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

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 sens...

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Published in:Journal of innate immunity Vol. 1; no. 2; pp. 153 - 163
Main Authors: Plüddemann, Annette, Mukhopadhyay, Subhankar, Sankala, Marko, Savino, Silvana, Pizza, Mariagrazia, Rappuoli, Rino, Tryggvason, Karl, Gordon, Siamon
Format: Journal Article
Language:English
Published: Basel, Switzerland S. Karger AG 01-01-2009
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Summary: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.
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Annette Plüddemann and Subhankar Mukhopadhyay contributed equally to this study.
ISSN:1662-811X
1662-8128
1662-8128
DOI:10.1159/000155227