CXCL16 influences the nature and specificity of CpG-induced immune activation.
Unmethylated CpG motifs are present at high frequency in bacterial DNA. They provide a danger signal to the mammalian immune system that triggers a protective immune response characterized by the production of Th1 and proinflammatory cytokines and chemokines. Although the recognition of CpG DNA by B cells and plasmacytoid dendritic cells is mediated by TLR 9, these cell types differ in their ability to bind and respond to structurally distinct classes of CpG oligonucleotides. This work establishes that CXCL16, a membrane-bound scavenger receptor, influences the uptake, subcellular localization, and cytokine profile induced by D oligonucleotides. This is the first example of a surface receptor modifying the cellular specificity and nature of the immune response mediated by an intracellular TLR.
Gursel
Mayda
M
Section of Retroviral Research, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Gursel
Ihsan
I
Mostowski
Howard S
HS
Klinman
Dennis M
DM
D019138:Antibodies, Blocking / Q000378:metabolism / Q000502:physiology; D001666:Binding Sites, Antibody; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism; D051116:Receptors, Scavenger / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000235:genetics
D019138:Antibodies, Blocking; C408982:CPG-oligonucleotide; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D051116:Receptors, Scavenger; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9