Syndecan-1 promotes Staphylococcus aureus corneal infection by counteracting neutrophil-mediated host defense

J Biol Chem. 2011 Feb 4;286(5):3288-97. doi: 10.1074/jbc.M110.185165. Epub 2010 Dec 2.

Abstract

Many microbial pathogens subvert cell surface heparan sulfate proteoglycans (HSPGs) to infect host cells in vitro. The significance of HSPG-pathogen interactions in vivo, however, remains to be determined. In this study, we examined the role of syndecan-1, a major cell surface HSPG of epithelial cells, in Staphylococcus aureus corneal infection. We found that syndecan-1 null (Sdc1(-/-)) mice significantly resist S. aureus corneal infection compared with wild type (WT) mice that express abundant syndecan-1 in their corneal epithelium. However, syndecan-1 did not bind to S. aureus, and syndecan-1 was not required for the colonization of cultured corneal epithelial cells by S. aureus, suggesting that syndecan-1 does not mediate S. aureus attachment to corneal tissues in vivo. Instead, S. aureus induced the shedding of syndecan-1 ectodomains from the surface of corneal epithelial cells. Topical administration of purified syndecan-1 ectodomains or heparan sulfate (HS) significantly increased, whereas inhibition of syndecan-1 shedding significantly decreased the bacterial burden in corneal tissues. Furthermore, depletion of neutrophils in the resistant Sdc1(-/-) mice increased the corneal bacterial burden to that of the susceptible WT mice, suggesting that syndecan-1 moderates neutrophils to promote infection. We found that syndecan-1 does not affect the infiltration of neutrophils into the infected cornea but that purified syndecan-1 ectodomain and HS significantly inhibit neutrophil-mediated killing of S. aureus. These data suggest a previously unknown bacterial subversion mechanism where S. aureus exploits the capacity of syndecan-1 ectodomains to inhibit neutrophil-mediated bacterial killing mechanisms in an HS-dependent manner to promote its pathogenesis in the cornea.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Corneal Diseases / microbiology*
  • Heparan Sulfate Proteoglycans / metabolism
  • Heparitin Sulfate / metabolism
  • Host-Pathogen Interactions / immunology*
  • Mice
  • Mice, Knockout
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / pathogenicity*
  • Syndecan-1 / physiology*

Substances

  • Heparan Sulfate Proteoglycans
  • Syndecan-1
  • Heparitin Sulfate