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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Aaron F. Carlin
  • Yung-Chi Chang
  • Thomas Areschoug
  • Gunnar Lindahl
  • Nancy Hurtado-Ziola
  • Charles C. King
  • Ajit Varki
  • Victor Nizet
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
Original languageEnglish
Pages (from-to)1691-1699
JournalJournal of Experimental Medicine
Volume206
Issue number8
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes