Thrombospondin-1 promotes cellular adherence of gram-positive pathogens via recognition of peptidoglycan

FASEB J. 2007 Oct;21(12):3118-32. doi: 10.1096/fj.06-7992com. Epub 2007 May 16.

Abstract

Thrombospondin-1 (TSP1) is a matricellular glycoprotein that has key roles in interactions between human cells and components of the extracellular matrix. Here we report a novel role for the lectin TSP1 in pathogen-host interactions. Binding assays and flow cytometric analysis demonstrate that Streptococcus pneumoniae and other gram-positive pathogens including S. pyogenes, Staphylococcus aureus, and Listeria monocytogenes interact specifically with human TSP1. We also show for the first time that host cell-bound TSP1 promotes adherence of gram-positive pathogens to human epithelial and endothelial cell lines. Pretreatment of bacteria with sodium periodate but not Pronase E substantially reduced TSP1-mediated bacterial adherence to host cells, suggesting that a glycoconjugate on the bacterial cell surface functions as the receptor for TSP1. Lipoteichoic acids did not affect TSP1-mediated adherence of S. pneumoniae to host cells. In contrast, attachment of S. pneumoniae and other gram-positive pathogens to host cells via TSP1 was blocked by soluble peptidoglycan, indicating recognition of bacterial peptidoglycan by TSP1. In conclusion, our results demonstrate that recognition of gram-positive pathogens by TSP1 promotes bacterial colonization of host tissue cells. In this scenario, peptidoglycan functions as adhesin and TSP1 acts as a molecular bridge linking gram-positive bacteria with receptors on the host cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Adhesion / physiology*
  • Blood Platelets / metabolism
  • CD36 Antigens / metabolism
  • Cell Line
  • Gram-Positive Bacteria / pathogenicity
  • Gram-Positive Bacteria / physiology*
  • Heparan Sulfate Proteoglycans / metabolism
  • Humans
  • Peptidoglycan / metabolism*
  • Phagocytes / metabolism
  • Phagocytosis / physiology
  • Thrombospondin 1 / metabolism*

Substances

  • CD36 Antigens
  • Heparan Sulfate Proteoglycans
  • Peptidoglycan
  • Thrombospondin 1