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

J Exp Med. 2009 Aug 3;206(8):1691-9. doi: 10.1084/jem.20090691. Epub 2009 Jul 13.

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 beta 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / metabolism
  • Antigens, CD / immunology*
  • Antigens, Differentiation, Myelomonocytic / immunology*
  • Binding Sites
  • Cell Adhesion
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Humans
  • Immunity, Innate
  • In Vitro Techniques
  • Lectins / immunology*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Leukocytes / microbiology
  • Mutation
  • N-Acetylneuraminic Acid / metabolism
  • Phagocytes / immunology*
  • Phagocytes / metabolism
  • Phagocytes / microbiology*
  • Phagocytosis
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Tyrosine Phosphatases / metabolism
  • Respiratory Burst
  • Streptococcus agalactiae / genetics
  • Streptococcus agalactiae / immunology*
  • Streptococcus agalactiae / pathogenicity*
  • Virulence / immunology

Substances

  • Antigens, Bacterial
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • DNA-Binding Proteins
  • Lectins
  • SIGLEC5 protein, human
  • beta protein, Streptococcus
  • streptococcal beta antigen
  • Protein Tyrosine Phosphatases
  • N-Acetylneuraminic Acid