Glycotope Sharing between Snail Hemolymph and Larval Schistosomes: Larval Transformation Products Alter Shared Glycan Patterns of Plasma Proteins

Abstract

Recent evidence supports the involvement of inducible, highly diverse lectin-like recognition molecules in snail hemocyte-mediated responses to larval Schistosoma mansoni. Because host lectins likely are involved in initial parasite recognition, we sought to identify specific carbohydrate structures (glycans) shared between larval S. mansoni and its host Biomphalaria glabrata to address possible mechanisms of immune avoidance through mimicry of elements associated with the host immunoreactivity. A panel of monoclonal antibodies (mABs) to specific S. mansoni glycans was used to identify the distribution and abundance of shared glycan epitopes (glycotopes) on plasma glycoproteins from B. glabrata strains that differ in their susceptibilities to infection by S. mansoni. In addition, a major aim of this study was to determine if larval transformation products (LTPs) could bind to plasma proteins, and thereby alter the glycotopes exposed on plasma proteins in a snail strain-specific fashion. Plasma fractions (<100 kDa/>100 kDa) from susceptible (NMRI) and resistant (BS-90) snail strains were subjected to SDS-PAGE and immunoblot analyses using mAB to LacdiNAc (LDN), fucosylated LDN variants, Lewis X and trimannosyl core glycans. Results confirmed a high degree of glycan sharing, with NMRI plasma exhibiting a greater distribution/abundance of LDN, F-LDN and F-LDN-F than BS-90 plasma (<100 kDa fraction). Pretreatment of blotted proteins with LTPs significantly altered the reactivity of specific mABs to shared glycotopes on blots, mainly through the binding of LTPs to plasma proteins resulting in either glycotope blocking or increased glycotope attachment to plasma. Many LTP-mediated changes in shared glycans were snail-strain specific, especially those in the <100 kDa fraction for NMRI plasma proteins, and for BS-90, mainly those in the >100 kDa fraction. Our data suggest that differential binding of S. mansoni LTPs to plasma proteins of susceptible and resistant B. glabrata strains may significantly impact early anti-larval immune reactivity, and in turn, compatibility, in this parasite-host system.

Digenean-gastropod host associations inform on aspects of specific immunity in snails

“…Several recent studies (Lehr et al, 2010; Yoshino et al, 2012, 2013) have shown that S. mansoni miracidia and sporocyst surface proteins and sporocyst transformation products bear glycan structures that are similar to those found expressed on plasma proteins or hemocytes of B. glabrata . This similarity adds significant additional evidence to a long-standing hypothesis (Damian, 1964) that parasites may escape immunological detection in their hosts by molecular mimicry.…”

“…This similarity adds significant additional evidence to a long-standing hypothesis (Damian, 1964) that parasites may escape immunological detection in their hosts by molecular mimicry. Further support for this idea comes from the observation that plasma proteins from susceptible strains of B. glabrata have a greater distribution and abundance of sharing of some glycans than plasma proteins from a schistosome resistant strain (Yoshino et al, 2012). This may in turn enable non-self detecting molecules circulating in snail plasma, including the diverse FREP plasma proteins (Zhang et al, 2004), to recognize sporocysts more readily in resistant snails.…”

“…Complexes of FREPs and polymorphic mucins from S. mansoni have been isolated (Moné et al, 2010), and studies of FREP3 knockdown snails have yielded phenotypes more susceptible to echinostome and schistosome infection (Hanington et al, 2010b, 2012). Diversified polymorphic mucin proteins, coupled with a large potential variety of glycan structures with which they may be adorned (Yoshino et al, 2012), could provide a huge repertoire of antigenic diversity to be countered by diversified recognition molecules like FREPs.…”

Glycoconjugates in Host-Helminth Interactions

“…Larval glycans and/or their associated glycoconjugates might also be serving as PAMPs that interact with lectin-like PRRs (284). PRRs, such as Toll receptors, C-type lectins, galectins, nucleic acid-sensing receptors, and the intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) occur both extracellularly and intracellularly, with the galectins notably found in both the cytoplasm and extracellularly (285).…”

“…During their development in the molluscan intermediate host, S. mansoni sporocysts release excretory/secretory glycoproteins that bind to lectin PRRs on the surface of the snail host hemocytes and are believed to modulate the ability of the hemocytes to interact with the developing larvae (279). The binding of glycoconjugates to B. glabrata hemocyte lectins can trigger the generation of parasite-killing reactive oxygen species, thereby mediating innate immune responses to invading miracidia (10, 275, 277, 280, 281, 284). …”