Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement

Elife. 2020 Sep 10;9:e60908. doi: 10.7554/eLife.60908.

Abstract

Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern-recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to Aspergillus fumigatus solely in a C3b-dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3-depleted serum. However, when opsonized with sCL-12, properdin bound in a C3-independent manner exclusively via its tetrameric structure and directed in situ C3bBb assembly. In conclusion, a prerequisite for properdin binding and in situ C3bBb assembly was the initial docking of sCL-12. This implies a new important function of properdin in host defense bridging pattern recognition and specific AP activation.

Keywords: alternative pathway; collectin-12; immunology; infectious disease; inflammation; microbiology; properdin; the complement system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus fumigatus / immunology
  • Collectins* / blood
  • Collectins* / metabolism
  • Complement C3 / metabolism
  • Complement Pathway, Alternative* / immunology
  • Complement Pathway, Alternative* / physiology
  • HEK293 Cells
  • Humans
  • Properdin* / analysis
  • Properdin* / metabolism
  • Protein Binding / immunology

Substances

  • Collectins
  • Complement C3
  • Properdin

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.