TY - JOUR
T1 - A soluble form of Siglec-9 provides a resistance against Group B Streptococcus (GBS) infection in transgenic mice
AU - Saito, Mitsumasa
AU - Yamamoto, Sayo
AU - Ozaki, Kinuyo
AU - Tomioka, Yukiko
AU - Suyama, Haruka
AU - Morimatsu, Masami
AU - Nishijima, Ken ichi
AU - Yoshida, Shin ichi
AU - Ono, Etsuro
N1 - Funding Information:
We thank Miyoko Endo, Tokyo Metropolitan Research Laboratory of Public Health, for providing us with GBS strains and Dr. J. Miyazaki for providing pCXN2 vector. This work was supported by Grant-in-Aid for Scientific Research (C) (Grant Number 26450398 ) from The Ministry of Education, Culture, Sports, Science and Technology of Japan .
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 × 103 CFU/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.
AB - 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 × 103 CFU/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.
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U2 - 10.1016/j.micpath.2016.08.014
DO - 10.1016/j.micpath.2016.08.014
M3 - Article
C2 - 27544323
AN - SCOPUS:84983070858
SN - 0882-4010
VL - 99
SP - 106
EP - 110
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
ER -
