Soluble CD163 promotes recognition, phagocytosis and killing of Staphylococcus aureus via binding of specific fibronectin peptides.
CD163 is a multi-ligand scavenger receptor exclusively expressed by monocytes and macrophages, which is released after their activation during sepsis (sCD163). The biological relevance of sCD163, however, is not yet clear. We now demonstrate that sCD163 exhibits direct antimicrobial effects by recognizing a specific subfragment ((6) F1(1) F2(2) F2(7) F1) of fibronectin (FN) bound to staphylococcal surface molecules. Moreover, contact with staphylococci promotes sCD163-shedding from monocyte surface via induction of metalloproteinases ADAM10 and ADAM17. sCD163 subsequently binds to Staphylococcus aureus via FN peptides and strongly amplifies phagocytosis as well as killing by monocytes and to a lesser extend by neutrophils. This mechanism exhibits additional paracrine effects because staphylococci additionally opsonized by sCD163 induce higher activation and more efficient killing activity of non-professional phagocytes like endothelial cells. Targeting pathogen-bound FN by sCD163 would be a very sophisticated strategy to attack S. aureus as any attempt of the pathogen to avoid this defence mechanism will automatically bring about loss of adherence to the host protein FN, which is a pivotal patho-mechanism of highly invasive staphylococcal strains. Thus, we report a novel function for sCD163 that is of particular importance for immune defence of the host against S. aureus infections.
Institute of Immunology, University of Münster, 48149 Münster, Germany.
Jessica
J
Kneidl
Bettina
B
Löffler
Michele C
MC
Erat
Julia
J
Kalinka
Georg
G
Peters
Johannes
J
Roth
Katarzyna
K
Barczyk
D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000378:metabolism; D050296:Microbial Viability; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D010587:Phagocytosis; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D017384:Sequence Deletion; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001425:Bacterial Outer Membrane Proteins; D000098902:CD163 Antigen; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human