title: C-reactive protein-mediated phagocytosis of Leishmania donovani promastigotes does not alter parasite survival or macrophage responses.
abstract: C-reactive protein (CRP) is an acute phase protein that binds to surface structures of a number of different organisms. Leishmania donovani express CRP ligand when first entering the mammalian host and CRP has been shown to alter macrophage function. The aim of this study was to investigate the functional significance of CRP-mediated uptake of L. donovani on survival of the parasite within human macrophages and macrophage cell responses to the infection. CRP opsonized L. donovani uptake was inhibitable by including excess CRP in the fluid phase, suggesting Fc receptor usage rather than indirect complement-mediated uptake. Comparing equivalent initial infection loads, parasite survival over 72 h within peripheral blood derived macrophages (PBMs) and differentiated U937 cells was unaltered by CRP. Whereas CRP increased macrophage responses to phosphorylcholine coated erythrocytes, no significant alteration in tumour necrosis factor-alpha, interleukin (IL)-10 or IL-12 production from PBMs was observed between CRP opsonized or unopsonized L. donovani promastigotes. Thus, in contrast to other systems, where CRP opsonization results in macrophage activation, Leishmania can use CRP to improve infection without inducing detrimental macrophage activation.
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. kikki.bodman-smith@lshtm.ac.uk
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Bodman-Smith
authors.forename: Margaret
authors.initials: M
authors.lastname: Mbuchi
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Culley
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bates
authors.forename: John G
authors.initials: JG
authors.lastname: Raynes
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D006801:Humans; D007893:Leishmania donovani / Q000254:growth & development* / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000469:parasitology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis; D020298:U937 Cells
chemical_list: D009895:Opsonin Proteins; D002097:C-Reactive Protein