CD93 is a cell surface lectin receptor involved in the control of the inflammatory response stimulated by exogenous DNA

Immunology. 2019 Oct;158(2):85-93. doi: 10.1111/imm.13100. Epub 2019 Jul 23.

Abstract

Bacterial DNA contains CpG oligonucleotide (ODN) motifs to trigger innate immune responses through the endosomal receptor Toll-like receptor 9 (TLR9). One of the cell surface receptors to capture and deliver microbial DNA to intracellular TLR9 is the C-type lectin molecule DEC-205 through its N-terminal C-type lectin-like domain (CTLD). CD93 is a cell surface protein and member of the lectin group XIV with a CTLD. We hypothesized that CD93 could interact with CpG motifs, and possibly serve as a novel receptor to deliver bacterial DNA to endosomal TLR9. Using ELISA and tryptophan fluorescence binding studies we observed that the soluble histidine-tagged CD93-CTLD was specifically binding to CpG ODN and bacterial DNA. Moreover, we found that CpG ODN could bind to CD93-expressing IMR32 neuroblastoma cells and induced more robust interleukin-6 secretion when compared with mock-transfected IMR32 control cells. Our data argue for a possible contribution of CD93 to control cell responsiveness to bacterial DNA in a manner reminiscent of DEC-205. We postulate that CD93 may act as a receptor at plasma membrane for DNA or CpG ODN and to grant delivery to endosomal TLR9.

Keywords: C-type lectin-like domain; CD93; CpG oligonucleotide; Toll-like receptor 9; bacterial DNA; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Biological Transport / genetics
  • Biological Transport / immunology
  • Cell Line, Tumor
  • Cloning, Molecular
  • DNA, Bacterial / genetics
  • DNA, Bacterial / immunology*
  • DNA, Bacterial / metabolism
  • Endosomes / immunology
  • Endosomes / metabolism
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Gene Expression Regulation / immunology*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Inflammation
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / immunology
  • Models, Biological
  • Neurons / immunology
  • Neurons / metabolism
  • Neurons / pathology
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / immunology*
  • Oligodeoxyribonucleotides / metabolism
  • Protein Binding
  • Protein Domains
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Complement / genetics
  • Receptors, Complement / immunology*
  • Receptors, Complement / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology*

Substances

  • Antigens, CD
  • CPG-oligonucleotide
  • DEC-205 receptor
  • DNA, Bacterial
  • IL6 protein, human
  • Interleukin-6
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Minor Histocompatibility Antigens
  • Oligodeoxyribonucleotides
  • Receptors, Cell Surface
  • Receptors, Complement
  • Recombinant Fusion Proteins
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • complement 1q receptor