title: Mice deficient in ficolin, a lectin complement pathway recognition molecule, are susceptible to Streptococcus pneumoniae infection.
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.
authors.affiliation: Department of Immunology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan. yendo@fmu.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Endo
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iwaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ishida
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakazawa
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kodama
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuzaka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kanno
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawamura
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
authors.forename: Ikuo
authors.initials: I
authors.lastname: Wada
authors.forename: Misao
authors.initials: M
authors.lastname: Matsushita
authors.forename: Wilhelm J
authors.initials: WJ
authors.lastname: Schwaeble
authors.forename: Teizo
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D016466:CHO Cells; D003167:Complement Activation / Q000235:genetics / Q000276:immunology*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics*; D006224:Cricetinae; D020022:Genetic Predisposition to Disease; D037102:Lectins / Q000172:deficiency* / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000172:deficiency / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011018:Pneumonia, Pneumococcal / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology*; D000097604:Ficolins
chemical_list: D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins