Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection

J Immunol. 2012 Dec 15;189(12):5860-6. doi: 10.4049/jimmunol.1200836. Epub 2012 Nov 12.

Abstract

Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine proteases, key enzymes of complement activation via the lectin pathway, and act as soluble pattern recognition molecules in the innate immune system. Although numerous reports have revealed the importance of MBL in infectious diseases and autoimmune disorders, the role of ficolin is still unclear. To define the specific role of ficolin in vivo, we generated model mice deficient in ficolins. The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera, because of the absence of complexes comprising FcnA and MBL-associated serine proteases. When the host defense was evaluated by transnasal infection with a Streptococcus pneumoniae strain, which was recognized by ficolins, but not by MBLs, the survival rate was significantly reduced in all three ficolin-deficient (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice. Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and ficolin B are essential in defense against S. pneumoniae. These results suggest that ficolins play a crucial role in innate immunity against pneumococcal infection through the lectin complement pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Complement Activation / genetics
  • Complement Activation / immunology*
  • Complement Pathway, Mannose-Binding Lectin / genetics*
  • Cricetinae
  • Ficolins
  • Genetic Predisposition to Disease*
  • Lectins / deficiency*
  • Lectins / genetics*
  • Mannose-Binding Protein-Associated Serine Proteases / deficiency
  • Mannose-Binding Protein-Associated Serine Proteases / genetics
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Pneumonia, Pneumococcal / enzymology
  • Pneumonia, Pneumococcal / genetics
  • Pneumonia, Pneumococcal / immunology*
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / immunology*

Substances

  • Lectins
  • Mannose-Binding Protein-Associated Serine Proteases