Controlled Chaos of Polymorphic Mucins in a Metazoan Parasite (Schistosoma mansoni) Interacting with Its Invertebrate Host (Biomphalaria glabrata)

Invertebrates were long thought to possess only a simple, effective and hence non-adaptive defence system against microbial and parasitic attacks. However, recent studies have shown that invertebrate immunity also relies on immune receptors that diversify (e.g. in echinoderms, insects and mollusks (Biomphalaria glabrata)). Apparently, individual or population-based polymorphism-generating mechanisms exists that permit the survival of invertebrate species exposed to parasites. Consequently, the generally accepted arms race hypothesis predicts that molecular diversity and polymorphism also exist in parasites of invertebrates. We investigated the diversity and polymorphism of parasite molecules (Schistosoma mansoni Polymorphic Mucins, SmPoMucs) that are key factors for the compatibility of schistosomes interacting with their host, the mollusc Biomphalaria glabrata. We have elucidated the complex cascade of mechanisms acting both at the genomic level and during expression that confer polymorphism to SmPoMuc. We show that SmPoMuc is coded by a multi-gene family whose members frequently recombine. We show that these genes are transcribed in an individual-specific manner, and that for each gene, multiple splice variants exist. Finally, we reveal the impact of this polymorphism on the SmPoMuc glycosylation status. Our data support the view that S. mansoni has evolved a complex hierarchical system that efficiently generates a high degree of polymorphism—a “controlled chaos”—based on a relatively low number of genes. This contrasts with protozoan parasites that generate antigenic variation from large sets of genes such as Trypanosoma cruzi, Trypanosoma brucei and Plasmodium falciparum. Our data support the view that the interaction between parasites and their invertebrate hosts are far more complex than previously thought. While most studies in this matter have focused on invertebrate host diversification, we clearly show that diversifying mechanisms also exist on the parasite side of the interaction. Our findings shed new light on how and why invertebrate immunity develops

RESEARCH NOTE - Biochemical Characterization of Cathepsin D from Adult Schistosoma mansoni Worms

Schistosomes ingest and lyse host blood cells, releasing the haemoglobin (Hb) into their gut. AR Timms and E Bueding found an acid protease activity in Schistosoma mansoni which was capable of hydrolysing Hb; they suggested that host Hb degradation provided the major amino acid source for the synthesis of parasite proteins. From 1979 on, Hb degradation by schistosomes was considered mostly due to cysteine proteinase (CP) activity. Several S. mansoni and S. japonicum CPs have been reported to be possibly involved in the degradation of this substrate which includes cathepsin B (Sm31, Sj31 antigens), cathepsin L and an asparaginyl endopeptidase (Sm32, Sj32 antigens). However, a proteinase-processing, rather than a direct Hb-digesting role for the Sm32 have been suggested by JP Dalton and PJ Brindley. On the other hand, cathepsin L has been mainly located in the reproductive system of the worms and it is present in smaller amount than cathepsin B in the adult worm vomitus of several Schistosoma species, suggesting a minor role of this enzyme in the digestion of Hb. An important proportion of the Hb degradation exerted by S. mansoni extracts occurs in the absence of thiols between pH 3.5 and 4.5 and this activity is inhibited by pepstatin A (a classic aspartyl proteinase inhibitor) but not by thiol-, serine- and metalloproteinase inhibitors. Using mercury-labeled pepstatin, BJ Bogitsh and KF Kirschner localized an aspartyl proteinase in the cecal lumen and to the gastrodermis of S. japonicum. Immunocytochemical studies using heterologous antiserum to bovine cathepsin D indicated that the S. japonicum cathepsin D-like enzyme is also localized to the dorsal and lateral surfaces of the tegument and tubercles of male worms. A cDNA encoding this proteinase was isolated and the native enzyme biochemically characterized at pH 3.5

Detection of Schistosoma mansoni Membrane Antigens by Immunoblot Analysis of Sera of Patients from Low-Transmission Areas

Schistosoma mansoni surface membrane components play a relevant role in the host-parasite interaction, and some are released in vivo as circulating antigens. n-Butanol extraction favors the release of membrane antigens like alkaline phosphatase, which has been shown to be specifically recognized by antibodies from S. mansoni-infected humans and animals. In the present study, components in the n-butanol extract (BE) of the adult S. mansoni worm membrane fraction were separated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE [15%]) and further analyzed by immunoblotting (immunoglobulin G) using defined sera. S. mansoni-infected patient sera, but not sera of uninfected patients or sera obtained from patients infected with other parasite species, specifically and variably recognized up to 20 polypeptides in the molecular mass range of ∼8 to >80 kDa. There were some differences in the number, intensity, and frequency of recognition of the BE antigens among sera from Venezuelan sites of endemicity with a different status of schistosomiasis transmission. Antigens in the 28- to 24-kDa molecular mass range appeared as immunodominants and were recognized by S. mansoni-positive sera from all the sites, with recognition frequencies varying between 57.5 and 97.5%. Immunoblotting with BE membrane antigens resulted in a highly sensitive (98.1%), specific (96.1.0%), and confirmatory test for the immunodiagnosis of schistosomiasis in low-transmission areas

Antigenic enzymes of Schistosoma mansoni: possible use for immunodiagnosis

Different enzymes of Schistosoma mansoni are recognized by IgG antibodies present in the sera of infected human patients. The antigenicity of these enzymes suggests their possible use in immunodiagnostic assays that would take advantage of their activities