A Large Repertoire of Parasite Epitopes Matched by a Large Repertoire of Host Immune Receptors in an Invertebrate Host/Parasite Model

Abstract

For many decades, invertebrate immunity was believed to be non-adaptive, poorly specific, relying exclusively on sometimes multiple but germ-line encoded innate receptors and effectors. But recent studies performed in different invertebrate species have shaken this paradigm by providing evidence for various types of somatic adaptations at the level of putative immune receptors leading to an enlarged repertoire of recognition molecules. Fibrinogen Related Proteins (FREPs) from the mollusc Biomphalaria glabrata are an example of these putative immune receptors. They are known to be involved in reactions against trematode parasites. Following not yet well understood somatic mechanisms, the FREP repertoire varies considerably from one snail to another, showing a trend towards an individualization of the putative immune repertoire almost comparable to that described from vertebrate adaptive immune system. Nevertheless, their antigenic targets remain unknown. In this study, we show that a specific set of these highly variable FREPs from B. glabrata forms complexes with similarly highly polymorphic and individually variable mucin molecules from its specific trematode parasite S. mansoni (Schistosoma mansoni Polymorphic Mucins: SmPoMucs). This is the first evidence of the interaction between diversified immune receptors and antigenic variant in an invertebrate host/pathogen model. The same order of magnitude in the diversity of the parasite epitopes and the one of the FREP suggests co-evolutionary dynamics between host and parasite regarding this set of determinants that could explain population features like the compatibility polymorphism observed in B. glabrata/S. mansoni interaction. In addition, we identified a third partner associated with the FREPs/SmPoMucs in the immune complex: a Thioester containing Protein (TEP) belonging to a molecular category that plays a role in phagocytosis or encapsulation following recognition. The presence of this last partner in this immune complex argues in favor of the involvement of the formed complex in parasite recognition and elimination from the host.

Role for a somatically diversified lectin in resistance of an invertebrate to parasite infection

“…FREPs change in abundance in snail hemolymph following digenean infection (15,35,36) and can precipitate secretory/excretory products of sporocysts implying they play a role in response to infections (15). FREPs have recently been shown to form complexes with highly polymorphic mucin molecules produced by S. mansoni sporocysts, complexes that also include thioester-containing proteins believed to favor phagocytosis and encapsulation responses (40). Previous analysis of genomic sequence variants of the first IgSF domain of FREP3 (exon 2 underlined in Fig.…”

“…2A) revealed that a limited number of germline alleles are somatically diversified by both gene conversion and point mutation, and that correspondingly diverse populations of FREP3 mRNAs are produced (3). High levels of variability in another subfamily of FREPs (FREP2) have also recently been independently reported (40).…”

Use of OmpU porins for attachment and invasion of Crassostrea gigas immune cells by the oyster pathogen Vibrio splendidus

“…As such, they are equipped with immune receptors and effectors involved in pathogen recognition and control. Recent advances in molluskpathogen interactions have shown the existence of highly diverse somatically generated receptors that give high specificity to pathogen recognition (16,17). So far, in oysters, recognition is mediated by germ-line encoded receptors, such as a β-integrin, involved in hemocyte phagocytosis (18); it was proposed to serve as a receptor for the major plasma protein, the extracellular superoxide dismutase Cg-EcSOD, which contains a RGD cellbinding domain (19).…”

Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host

“…Studies investigating compatibility between Biomphalaria snails and S. mansoni suggest that the snail immune response plays a crucial role in determining infection outcome. Although circulating humoral factors are known to play an important role in determining infection outcome via recognition of various parasite targets, or by directly damaging the parasite tegument (1)(2)(3)(4), it is ultimately the immune cells of the snail, known as hemocytes, that are primarily responsible for encapsulating and eliminating the parasite (5).…”