Antibodies to tyvelose exhibit multiple modes of interference with the epithelial niche of Trichinella spiralis

Infection with the parasitic nematode Trichinella spiralis is initiated whe n the L1 larva invades host intestinal epithelial cells, Monoclonal antibod ies specific far glycans on the larval surface and secreted glycoproteins p rotect the intestine against infection, Protective antibodies recognize tyv elose which caps the target glycan. In this study, se used an in vitro mode l of invasion to further examine the mechanism(s) by which tyvelose-specifi c antibodies protect epithelial cells against T,spiralis, Using cell lines that vary in susceptibility to invasion, we confirmed and clarified the res ults of our in vivo studies by documenting three modes of interference: exc lusion of larvae from cells, encumbrance of larvae as they migrated within epithelial monolayers, and inhibition of parasite development. Excluded lar vae bear cephalic caps (C, S, McVay ct at., infect, Immun, 66:1941-1945, 19 98) of immune complexes that may. physically black invasion or may interfer e with sensory reception, Monovalent Fab fragments prepared from a tyvelose -specific antibody also excluded larvae from cells, demonstrating that anti body binding can inhibit the parasite in the absence of antigen aggregation and cap formation. In contrast, encumbered larvae caused extensive damage to the monolayer yet were not successful in establishing a niche, as reflec ted by their failure to molt. These results show that antibodies to tyvelos e exhibit multiple modes of inhibitory activity, further implicating tyvelo se-bearing glycoproteins as mediators of invasion and niche establishment b y T, spiralis.