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 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.