Infection by Trypanosoma cruzi - Identification of a parasite ligand and its host cell receptor

The infective trypomastigote stage of Trypanosoma cruzi expresses a set of surface glycoproteins that are known collectively as Tc85 and belong to the gp85/transsialidase supergene family. A member of this family, Tc85-11, wi th adhesive properties to laminin and cell surfaces was recently cloned. In this report, the Tc85-11 domain for cell binding and its corresponding rec eptor on epithelial cell LLC-MK2 are described. Using synthetic peptides co rresponding to the Tc85-11 carboxyl-terminal segment, we show that the mamm alian cell-binding domain colocalizes to the most conserved motif of the tr ypanosome gp85/trans-sialidase supergene family (VTVXNVFLYNR), Even though Tc85-11 binds to laminin, the 19-residue cell-binding peptide (peptide J) d oes not contain the laminin-binding site, because it does not bind to lamin in or inhibit cell binding to this glycoprotein, The host cell receptor for the peptide was characterized as cytokeratin 18, Addition of anti-cytokera tin antibodies to the culture medium significantly inhibited the infection of epithelial cells by T. cruzi. Tc85-11 is a multiadhesive glycoprotein, e ncoding at least two different binding sites, one for laminin and one for c ytokeratin 18, that allow the parasite to overcome the barriers imposed by cell membranes, extracellular matrices, and basal laminae to reach the defi nitive host cell. This is the first description of a direct interaction bet ween cytokeratin and a protozoan parasite.