A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q

Cell. 2006 Apr 7;125(1):47-58. doi: 10.1016/j.cell.2006.01.046.


The intricate system of serum complement proteins provides resistance to infection. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial binding C3 fragments recognized by leukocytes. The spleen and C3 provide resistance against blood-borne S. pneumoniae infection. To better understand the mechanisms involved, we studied SIGN-R1, a lectin that captures microbial polysaccharides in spleen. Surprisingly, conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-R1(+) spleen macrophages, and formation of C3 ligands. We found that SIGN-R1 directly bound the complement C1 subcomponent, C1q, and assembled a C3 convertase, but without the traditional requirement for either antibody or factor B. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen-Antibody Reactions / immunology
  • CHO Cells
  • Cell Adhesion Molecules / metabolism*
  • Complement Activation / immunology*
  • Complement C1q / immunology*
  • Complement C1q / metabolism*
  • Complement C3 / chemistry
  • Complement C3 / metabolism
  • Complement Pathway, Classical / immunology
  • Cricetinae
  • Cricetulus
  • Fibroblasts / cytology
  • Humans
  • Lectins, C-Type / metabolism*
  • Macrophages / cytology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polysaccharides, Bacterial / immunology*
  • Protein Binding
  • Receptors, Cell Surface / metabolism*
  • Spleen / cytology
  • Streptococcus pneumoniae / immunology*


  • Cell Adhesion Molecules
  • Complement C3
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Polysaccharides, Bacterial
  • Receptors, Cell Surface
  • Complement C1q