C-reactive protein binds to a novel ligand on Leishmania donovani and increases uptake into human macrophages

C-reactive protein (CRP) is a major acute phase protein of man, with serum concentrations increasing dramatically following stimulation of hepatocytes by inflammatory cytokines. However, the role of CRP in inflammation and resistance to infection is still poorly understood. Here, the specificity of CRP binding to the surface of Leishmania donovani, an obligate intracellular parasite of mononuclear phagocytes, is described. CRP is shown to bind to promastigotes at the infectious metacyclic stage of development, at concentrations found in normal human serum. The presence of CRP on the surface of promastigotes substantially increases uptake into human monocyte-derived macrophages. Unusually, CRP does not bind via its characteristic ligand, phosphorylcholine. We show that CRP binds to the lipophosphoglycan (LPG) component of the promastigote cell surface, a molecule implicated in both uptake and survival of these parasites within the macrophage, and also to the major secreted protein of promastigotes, secreted acid phosphatase. Using mAb to LPG with known ligand specificities, we define a novel ligand for CRP as the repeating phosphorylated disaccharide units that form the backbone of LPG.