A family of fibrinogen-related proteins that precipitates parasite-derived molecules is produced by an invertebrate after infection

Abstract

After infection with the digenetic trematode Echinostoma paraensei, hemolymph of the snail Biomphalaria glabrata contains lectins comprised of 65-kDa subunits that precipitate polypeptides secreted by E. paraensei intramolluscan larvae. Comparable activity is lacking in hemolymph of uninfected snails. Three different cDNAs with sequence similarities to peptides derived from the 65-kDa lectins were obtained and unexpectedly found to encode fibrinogen-related proteins (FREPs). These FREPs also contained regions with sequence similarity to Ig superfamily members. B. glabrata has at least five FREP genes, three of which are expressed at increased levels after infection. Elucidation of components of the defense system of B. glabrata is relevant because this snail is an intermediate host for Schistosoma mansoni, the most widely distributed causative agent of human schistosomiasis. These results are novel in suggesting a role for invertebrate FREPs in recognition of parasite-derived molecules and also provide a model for investigating the diversity of molecules functioning in nonself-recognition in an invertebrate.

Reconstructing immune phylogeny: new perspectives

“…The germline-diversified V domains in NITRs are an example of an adaptive immune feature in an innate immune receptor 73,74 , whereas germline joining of immunoglobulin-gene clusters in cartilaginous fish is an example of an innate immune feature in an adaptive immune receptor 18 . The Dscam variants in insects 10 , the FREPs in snails 8,126 , the VLRs in the jawless vertebrates lampreys 9 and hagfish 99 , and the VCBPs in the protochordate amphioxus 7,113 all share certain fundamental characteristics with the adaptive antigen-binding immune receptors of jawed vertebrates.…”

“…The expression of FREPs is upregulated on infection with a trematode (a type of parasitic flatworm); FREPs then bind to trematode sporocysts and precipitate soluble parasite-derived products from solution 126 . At the molecular level, FREPs consist of one or two tandem IgSF domains at the N terminus, as well as a fibrinogen-like domain at the C terminus, and they have lectin-like activity 126,127 ( carrying transallelic hypomorphic and amorphic mutations had reduced Dscam expression and less efficient phagocytosis of pathogenic bacteria, which was also achieved using Dscam-specific antibody and in RNA-interference studies.…”

“…The expression of FREPs is upregulated on infection with a trematode (a type of parasitic flatworm); FREPs then bind to trematode sporocysts and precipitate soluble parasite-derived products from solution 126 . At the molecular level, FREPs consist of one or two tandem IgSF domains at the N terminus, as well as a fibrinogen-like domain at the C terminus, and they have lectin-like activity 126,127 (TABLE 2).…”

“…The expression of FREPs is upregulated on infection with a trematode (a type of parasitic flatworm); FREPs then bind to trematode sporocysts and precipitate soluble parasite-derived products from solution 126 . At the molecular level, FREPs consist of one or two tandem IgSF domains at the N terminus, as well as a fibrinogen-like domain at the C terminus, and they have lectin-like activity 126,127 (TABLE 2). Fibrinogen is associated with blood coagulation in vertebrates; proteins that contain fibrinogen-like domains have previously been implicated in innate immune-defence functions in vertebrates and invertebrates 128 .…”

“…The germline-diversified V domains in NITRs are an example of an adaptive immune feature in an innate immune receptor 73,74 , whereas germline joining of immunoglobulin-gene clusters in cartilaginous fish is an example of an innate immune feature in an adaptive immune receptor 18 . The Dscam variants in insects 10 , the FREPs in snails 8,126 , the VLRs in the jawless vertebrates lampreys 9 and hagfish 99 , and Our historical considerations of the evolution of adaptive immunity have centred on the origins of the adaptive antigen-binding immune receptors themselves, as well as the MHC class I and class II molecules on which T-cell function depends so closely and the origins in phylogeny of which seem to coincide with the emergence of the antigen-binding receptors. Many efforts have been undertaken to label 'primordial' antigen-binding receptors in species outside the jawed vertebrates, under the presumption that such molecules exist and would appear in a recognizable form today.…”