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

Claudia Rennemeier^*,1, Sven Hammerschmidt^*,1,2, Silke Niemann, Seiichi Inamura, Ulrich Zähringer and Beate E. Kehrel

^* University of Wuerzburg, Research Center for Infectious Diseases, Wuerzburg, Germany;

Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University Hospital Muenster, Muenster, Germany; and

Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany

²Correspondence: Max von Pettenkofer-Institute for Hygiene and Microbiology, Ludwig-Maximilians University Munich, Pettenkoferstrasse 9a, D-80336 Muenchen, Germany. E-mail: hammerschmidt{at}mvp.uni-muenchen.de

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.—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.

Key Words: colonization • platelet lectin • pneumococci • staphylococci • host tissue cells