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Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5

Carlin, Aaron F.; Chang, Yung-Chi; Areschoug, Thomas LU ; Lindahl, Gunnar LU ; Hurtado-Ziola, Nancy; King, Charles C.; Varki, Ajit and Nizet, Victor (2009) In Journal of Experimental Medicine 206(8). p.1691-1699
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), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall-anchored beta protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of... (More)
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), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall-anchored beta protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS. protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
206
issue
8
pages
1691 - 1699
publisher
Rockefeller University Press
external identifiers
  • wos:000268598800008
  • scopus:68149179246
ISSN
1540-9538
DOI
10.1084/jem.20090691
language
English
LU publication?
yes
id
92c793e4-df77-4e64-b7a9-2009d19f5559 (old id 1459929)
date added to LUP
2009-08-31 10:41:14
date last changed
2017-12-10 04:08:03
@article{92c793e4-df77-4e64-b7a9-2009d19f5559,
  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), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall-anchored beta protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS. protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.},
  author       = {Carlin, Aaron F. and Chang, Yung-Chi and Areschoug, Thomas and Lindahl, Gunnar and Hurtado-Ziola, Nancy and King, Charles C. and Varki, Ajit and Nizet, Victor},
  issn         = {1540-9538},
  language     = {eng},
  number       = {8},
  pages        = {1691--1699},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5},
  url          = {http://dx.doi.org/10.1084/jem.20090691},
  volume       = {206},
  year         = {2009},
}