Role of heparan sulfate in interactions of Listeria monocytogenes with enterocytes.

Heparan sulfate is known to participate in binding a wide variety of microbes to mammalian cells, but few studies have focused on the enterocyte. Normal human colonic and small intestinal enterocytes, and cultured HT-29 (but not Caco-2) enterocytes, reacted prominently with antibodies specific for heparan sulfate and for the core protein of syndecan-1 (a heparan sulfate proteoglycan). The heparan sulfate analog, heparin, inhibited interactions of Listeria monocytogenes (adherence and internalization) with HT-29, but not Caco-2, enterocytes. Internalization of L. monocytogenes by HT-29 enterocytes was inhibited by heparan sulfate and to a lesser extent by chondroitin sulfate, but not by the non-sulfated glycosaminoglycan hyaluronic acid. Compared to plasmid control ARH-77 cells, adherence of L. monocytogenes, was increased using ARH-77 cells transfected with syndecan-1 cDNA. Heparin binding protein(s) on L. monocytogenes were confirmed using biotinylated heparin. To determine if these in vitro observations might have in vivo relevance, L. monocytogenes was preincubated with heparin and then orally inoculated into mice. Compared to L. monocytogenes not pretreated with heparin, L. monocytogenes pretreated with heparin was associated with decreased extraintestinal dissemination to the mesenteric lymph nodes and liver of orally inoculated mice. Thus, heparan sulfate (possibly as the heparan sulfate proteoglycan syndecan-1) appears to participate in interactions of L. monocytogenes with enterocytes.