Eicosanoids as immunomodulators of penetration by Schistosome cercariae

To infect a definitive host, schistosome cercorioe must identify and penetrate intact skin. This involves complex biochemical and morphological changes over a fairly brief time (48 hours), and possibly offers a potential point of intervention against infection. Attempts to define a vaccine against the invading organisms have so far been unsuccessful, but unravelling the complex biochemical interactions of schistosome penetration and transformation seems to suggest possible pharmacological or immunopharmacological interventions against these initial stages of infection.     

Schistosome carbohydrates

Schistosomes are long-lived in their human hosts (with life-spans measured in years), despite being situated in the blood stream and therefore apparently fully exposed to a wide range of vigorous immunological responses. However, not only have these parasites evolved so as to prosper in the hostile environment of their definitive host, but they also have to negotiate very different environments during the free-living and intermediate host stages of their life cycle. At each stage, surface, or secreted carbohydrates appear to play an important role in the parasite's interaction with its environment.     

Schistosome glysoconjugates

Schistosomes are trematodes known as blood flukes that cause schistosomiasis in people and animals. The male and female worms reside mainly in intestinal veins where they lay eggs that result in a wide-ranging pathology in infected individuals. A growing body of evidence indicates that carbohydrates on glycoproteins, glycolipids and glycosaminoglycans synthesized by the parasite are targets of humoral immunity and may play a role in modulating host immune responses. Carbohydrate antigens may provide protective immunity against infection. In addition, recent evidence indicates that glycoconjugates and carbohydrate-binding proteins from the parasites and their hosts participate in egg adhesion and granuloma formation involved in disease pathology. This review will highlight our current knowledge of the glycoconjugates synthesized by the parasites and their immunological and biological properties. There is increasing anticipation in the field that information about the glycobiology of these parasites may lead to carbohydrate-based vaccines and diagnostics for the disease and perhaps new therapies for treating infected individuals.     

Schistosome proteases

While studies of schistosome antigens have proceeded rapidly over the past ten years, studies of schistosome enzymes have also been increasing apace. Now the two `lines' of research are coming together. Parasites such as schistosomes hardly present antigens merely to stimulate a host immune response, so it is not surprising that many antigens turn out to have functions, for example, as enzymes. One type of antigenic schistosome enzyme - glutathione S-transferase - already shows promise as a vaccine candidate. Here, Jim McKerrow and Mike Doenhoff review another important class of enzyme, many of which are clearly antigenic, the schistosome proteases.     

Schistosome female reproductive development

Schistosome parasites have evolved to produce a number of unique features in their life history; one of these is separate sexes. This has, in turn, led to a novel interplay between the male and female parasite that has been recognized for over 50 years: the growth and reproductive development of the female parasite is in some way regulated by the male schistosome. Early classical and later experimental studies established that the presence of the male schistosome is necessary not only for the initiation of female development but also for the maintenance of her mature state. The male parasite regulates the reproductive development of the female, partly by providing a stimulus that is necessary for the development of the vitelline gland. The cells of the vitelline gland provide nutrients and shell precursors for the egg. Also in this review by Philip LoVerde and Li-ly Chen, it is interesting to note that recent molecular studies have confirmed early work by showing that gene expression in the female parasite is developmentally regulated in a tissue-specific manner and that this gene expression is controlled by the presence of a male parasite.     

Differential Expression of microRNAs in the Non-Permissive Schistosome Host Microtus fortis under Schistosome Infection

The reed vole Microtus fortis is the only mammal known in China in which the growth, development and maturation of schistosomes (Schistosoma japonicum) is prevented. It might be that the anti-schistosomiasis mechanisms of M. fortis associate with microRNA-mediated gene expression, given that the latter has been found to be involved in gene regulation in eukaryotes. In the present study, the difference between pathological changes in tissues of M. fortis and of mice (Mus musculus) post-schistosome infection were observed by using hematoxylin-eosin staining. In addition, microarray technique was applied to identify differentially expressed miRNAs in the same tissues before and post-infection to analyze the potential roles of miRNAs in schistosome infection in these two different types of host. Histological analyses showed that S. japonicum infection in M. fortis resulted in a more intensive inflammatory response and pathological change than in mice. The microarray analysis revealed that 162 miRNAs were expressed in both species, with 12 in liver, 32 in spleen and 34 in lung being differentially expressed in M. fortis. The functions of the differentially expressed miRNAs were mainly revolved in nutrient metabolism, immune regulation, etc. Further analysis revealed that important signaling pathways were triggered after infection by S. japonicum in M. fortis but not in the mice. These results provide new insights into the general mechanisms of regulation in the non-permissive schistosome host M. fortis that exploits potential miRNA regulatory networks. Such information will help improve current understanding of schistosome development and host–parasite interactions.     

Schistosome glycoconjugates in host-parasite interplay

Schistosomes are digenetic trematodes which cause schistosomiasis, also known as bilharzia, one of the main parasitic infections in man. In tropical and subtropical areas an estimated 200 million people are infected and suffer from the debilitating effects of this chronic disease. Schistosomes live in the blood vessels and strongly modulate the immune response of their host to be able to survive the hostile environment that they are exposed to. It has become increasingly clear that glycoconjugates of schistosome larvae, adult worms and eggs play an important role in the evasion mechanisms that schistosomes utilise to withstand the immunological measures of the host. Upon infection, the host mounts innate as well as adaptive immune responses to antigenic glycan elements, setting the immunological scene characteristic for schistosomiasis. In this review we summarise the structural data now available on schistosome glycans and provide data and ideas regarding the role that these glycans play in the various aspects of the glycobiology and immunology of schistosomiasis.     

Schistosome membrane proteins as vaccines

Schistosomes are parasitic blood flukes that infect approximately 200 million people and are arguably the most important human helminth in terms of mortality. The outermost surface of intra-mammalian stages of the parasite, the tegument, is the key to the parasite's success, but it is also generally viewed as the most susceptible target for vaccines and drugs. Over the past 2 years the proteome of the Schistosoma mansoni tegument has been investigated and these studies revealed surprisingly few proteins that are predicted to be accessible to the host immune response, namely proteins with at least one membrane-spanning domain. However, of this handful of proteins, some are showing great promise as recombinant vaccines against schistosomiasis at a pre-clinical level. In particular, the tetraspanin family of integral membrane proteins appears to be abundantly represented in the tegument, and convergent data using the mouse vaccine model and correlates of protective immunity in naturally exposed people suggests that this family of membrane proteins offer great promise for schistosomiasis vaccines. With the recent advances in schistosome genomics and proteomics, a new suite of potential vaccine antigens are presented and these warrant detailed investigation and appropriate funding over the next few years.     

Schistosome/mollusk: genetic compatibility

Schistosomiasis remains one of the most prevalent parasitic infections and has significant economic and public health consequences in many developing countries. Economic development and improvement in standard of living in these countries are dependent on the elimination of this odious disease. For the control of Schistosomiasis, understanding the host/parasite association is important, since the host parasite relationship is often complex and since questions remain concerning the susceptibility of snails to infection by respective trematodes and their specificity and suitability as hosts for continued parasite development. Thus, the long term aim of this research is to learn more about the genetic basis of the snail/parasite relationship with the hope of finding novel ways to disrupt the transmission of this disease. In the current research, genetic variability among susceptible and resistant strains within and between Biomphalaria glabrata and B. tenagophila was investigated using RAPD-PCR. The results indicate great genetic variations within the two snail species using three different primers (intrapopulational variations), while specimens from the same snail species showed few individual differences between the susceptible and resistant strains (interpopulational variation).     

Schistosome infection promotes osteoclast-mediated bone loss

Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4⁺ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.