Thrombospondin‐1 promotes cellular adherence of Gram‐positive pathogens via recognition of peptidoglycan

Thrombospondin‐1 (TSP1) is a matri‐cellular 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. Pretreat‐ment of bacteria with sodium periodate but not Pronase E substantially reduced TSP1‐mediated bacterial adherence to host cells, suggesting that a glycoconju‐gate 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 Grampositive pathogens by TSP1 promotes bacterial colonization of host tissue cells. In this scenario, pep‐tidoglycan functions as adhesin and TSP1 acts as a molecular bridge linking Gram‐positive bacteria with receptors on the host cell.—Rennemeier, C., Hammerschmidt, S., Niemann, S., Inamura, S., Zähringer, U., Kehrel, B. E. Thrombospondin‐1 promotes cellular adherence of Gram‐positive pathogens via recognition of peptidoglycan. FASEB J. 21, 3118–3132 (2007)