title: Thrombospondin-1 promotes cellular adherence of gram-positive pathogens via recognition of peptidoglycan.
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.
authors.affiliation: University of Wuerzburg, Research Center for Infectious Diseases, Wuerzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rennemeier
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: Silke
authors.initials: S
authors.lastname: Niemann
authors.forename: Seiichi
authors.initials: S
authors.lastname: Inamura
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.forename: Beate E
authors.initials: BE
authors.lastname: Kehrel
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D006094:Gram-Positive Bacteria / Q000472:pathogenicity / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D010457:Peptidoglycan / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D019700:Thrombospondin 1 / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D019812:Heparan Sulfate Proteoglycans; D010457:Peptidoglycan; D019700:Thrombospondin 1