C1q/TNF-Related Protein 6 Is a Pattern Recognition Molecule That Recruits Collectin-11 from the Complement System to Ligands

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  • Nikolaj Kirketerp-Møller
  • Rafael Bayarri-Olmos
  • Karen Angeliki Krogfelt
  • Garred, Peter

C1q/TNF-related protein (CTRP) 6 is a member of the CTRP protein family associated with the regulation of cellular and endocrine processes. CTRP6 contains collagen and globular structures, resembling the pattern recognition molecules (PRMs) of the classical and lectin complement pathways. We expressed human CTRP6 in Chinese hamster ovary cells and investigated the binding to different putative ligands (acetylated BSA [AcBSA], zymosan, mannan, and LPS from Escherichia coli and Salmonella as well as to the monosaccharides l-fucose, d-mannose, N-acetylglucosamine, N-acetylgalactosamine, and galactose). Furthermore, we investigated the binding of CTRP6 to various Gram-negative bacteria as well as PRMs and enzymes of the lectin complement pathway. We found that CTRP6 bound to AcBSA and to a lesser extent to zymosan. Using EDTA as chelating agent, we observed an increased binding to AcBSA, zymosan and the two strains of LPS. We detected no binding to mannan and BSA. We identified l-fucose as a ligand for CTRP6 and that it bound to certain enteroaggregative Escherichia coli and Pseudomonas aeruginosa isolates, whereas to other bacterial isolates, no binding was observed. CTRP6 did not appear to interact directly with the activating enzymes of the lectin pathway; however, we could show the specific recruitment of collectin-11 and subsequent initiation of the complement cascade through deposition of C4. In conclusion, our results demonstrate the binding of CTRP6 to a variety of microbial and endogenous ligands identifying CTRP6 as a novel human lectin and PRM of importance for complement recognition and innate immunity.

Original languageEnglish
JournalJournal of Immunology
Volume204
Issue number6
Pages (from-to)1598-1606
ISSN0022-1767
DOIs
Publication statusPublished - 2020

Bibliographical note

Copyright © 2020 by The American Association of Immunologists, Inc.

    Research areas

  • Animals, Antigens, Bacterial/immunology, CHO Cells, Collagen/genetics, Collectins/metabolism, Complement Activation, Complement C4/metabolism, Complement Pathway, Mannose-Binding Lectin/immunology, Cricetulus, Escherichia coli/immunology, Ligands, Mannose-Binding Protein-Associated Serine Proteases/metabolism, Pseudomonas aeruginosa/immunology, Recombinant Proteins/genetics

ID: 269533359