title: A soluble form of Siglec-9 provides a resistance against Group B Streptococcus (GBS) infection in transgenic mice.
abstract: Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), possessing terminal sialic acid residues that suppress host immune response and provide a survival advantage to the pathogen. CPS binds to Siglec-9 expressed on neutrophils, which is expected to down-regulate the immune responsiveness of neutrophils. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of CPS to Siglec-9 on immune cells, leading to provide antibacterial benefit against GBS infection in the transgenic mouse line expressing sSiglec-9 (sSiglec-9 Tg). The sSiglec-9 in the sera of sSiglec-9 Tg bound to the sialylated-GBS strains belonging to serotypes Ia, Ib, II, III, IV and V in whole GBS cell ELISA. When GBS cells of serotype III that is a common serotype in late-onset GBS disease (LOD) were intraperitoneally inoculated into sSiglec-9 Tg, sSiglec-9 Tg showed a significant resistance as compared with non-transgenic littermates. Furthermore, GBS serotype III organisms were not detected in cultures of the blood from surviving mice (<1 × 103CFU/ml). These results indicated that sSiglec-9 Tg mice were more efficient in eliminating GBS and survived better after the intraperitoneal challenge with GBS serotype III bacteria.
authors.affiliation: Department of Microbiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: msaito@med.uoeh-u.ac.jp.
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Saito
authors.affiliation: Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: ysayo@anim.med.kyushu-u.ac.jp.
authors.forename: Sayo
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: k-ozaki@anim.med.kyushu-u.ac.jp.
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: Department of Laboratory Animal Science, Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. Electronic address: ytomi@muses.tottori-u.ac.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tomioka
authors.affiliation: Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: sharuka@anim.med.kyushu-u.ac.jp.
authors.forename: Haruka
authors.initials: H
authors.lastname: Suyama
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Electronic address: mmorimat@vetmed.hokudai.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Morimatsu
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: nishijma@nubio.nagoya-u.ac.jp.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Nishijima
authors.affiliation: Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: syn-ichi@bact.med.kyushu-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Yoshida
authors.affiliation: Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Biomedicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: etsuro@anim.med.kyushu-u.ac.jp.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ono
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D060467:Disease Resistance; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018805:Sepsis / Q000276:immunology* / Q000517:prevention & control*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism*; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D013292:Streptococcus agalactiae / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
keywords: Antibacterial benefit; Group B Streptococcus; Soluble Siglec-9; Transgenic mice