Comparative Vectorial Competence of Biomphalaria sudanica and Biomphalaria choanomphala, Snail Hosts of Schistosoma mansoni, From Transmission Hotspots In Lake Victoria, Western Kenya.

Schistosoma mansoni, which causes human intestinal schistosomiasis, continues to be a major public health concern in the Lake Victoria basin in western Kenya, with Biomphalaria sudanica (a shoreline inhabiting snail) and Biomphalaria choanomphala (a deep-water snail) playing roles in transmission. A recent study showed that B. sudanica was abundantly present near all study villages on the lakeshore, but B. choanomphala was significantly more abundant near villages known to be persistent transmission hotspots. The present study investigated the relative compatibility of B. sudanica and B. choanomphala with S. mansoni. A reciprocal cross-infection experiment used young adult F1 generation B. sudanica and B. choanomphala that were exposed to either 1, 5, or 10 sympatric or allopatric human-derived S. mansoni miracidia. Three weeks post-exposure (PE) and weekly thereafter, the snails were counted and screened for schistosome cercariae, and at 7 wk PE, total cercariae shed during a 2 hr period by each infected snail was determined. Pre-patent periods for S. mansoni in both B. sudanica and B. choanomphala were similar, and most snails in all exposure combinations started shedding cercariae 5 wk PE. Prevalences were significantly higher in B. choanomphala (12.2-80.9%) than in B. sudanica (5.2-18.6%) at each dose, regardless of whether miracidia were of an allopatric or a sympatric source (P < 0.0001). Overall, the odds of a snail becoming infected with 5 or 10 miracidia were significantly higher than the odds of being infected with 1 miracidium, (P < 0.0001), and fewer cercariae were produced by snails exposed to single as compared to 5 or 10 miracidia. On average, B. choanomphala produced more cercariae ( = 458, SD = 414) than B. sudanica ( = 238, SD = 208) (P < 0.0001). These results suggest that B. choanomphala is more compatible with S. mansoni than B. sudanica. Though B. choanomphala can be found in shallow shoreline waters, it is, for the most part, a deeper-water taxon. Because dredging is a relatively inefficient means of sampling, B. choanomphala is likely underestimated with respect to its population size, the number of S. mansoni-positive snails, and its role in maintaining transmission.

Effect of methyl gallate on immune response of Biomphalaria alexandrina (Ehrenberg, 1831) snails to infection with Schistosoma mansoni (Sambon, 1907).

Schistosomiasis still affects a lot of people in many developing countries. Reducing the disease dissemination has been the target of various studies. As methyl gallate has antioxidant properties, it is assumed that it can be a good candidate for stimulating the immune response of snails. So, the aim of this work is to investigate the potential of using methyl gallate as an immunostimulant to Biomphalaria alexandrina snails in order to prevent the development of invading miracidia into infective cercariae. The infected snails were exposed to three concentrations of methyl gallate for two periods: 24 and 72 h. The results indicated that the most effective concentration was the lowest one: 125 mg/L of methyl gallate for 72 h, as it reduced both infection rate and mean number of shed cercariae. Also, it increased the total number of snails' hemocytes in hemolymph, which were observed in head-foot region and digestive gland of treated snails surrounding degenerated sporocysts and cercariae. In addition, hydrogen peroxide showed its highest content in tissues of snails exposed to 125 mg/L of methyl gallate for 72 h. In conclusion, methyl gallate can be considered as one of the most promising immunostimulants of B. alexandrina snails against infection with Schistosoma mansoni.

Genomic and transcriptional analysis of genes containing fibrinogen and IgSF domains in the schistosome vector Biomphalaria glabrata, with emphasis on the differential responses of snails susceptible or resistant to Schistosoma mansoni.

Achieving a deeper understanding of the factors controlling the defense responses of invertebrate vectors to the human-infecting pathogens they transmit will provide needed new leads to pursue for control. Consequently, we provide new genomic and transcriptomic insights regarding FReDs (containing a fibrinogen domain) and FREPs (fibrinogen domain and one or two IgSF domains) from the planorbid snail Biomphalaria glabrata, a Neotropical vector of Schistosoma mansoni, causative agent of human intestinal schistosomiasis. Using new bioinformatics approaches to improve annotation applied to both genome and RNA-Seq data, we identify 73 FReD genes, 39 of which are FREPs. We provide details of domain structure and consider relationships and homologies of B. glabrata FBG and IgSF domains. We note that schistosome-resistant (BS-90) snails mount complex FREP responses following exposure to S. mansoni infection whereas schistosome-susceptible (M line) snails do not. We also identify several coding differences between BS-90 and M line snails in three FREPs (2, 3.1 and 3.2) repeatedly implicated in other studies of anti-schistosome responses. In combination with other results, our study provides a strong impetus to pursue particular FREPs (2, 3.1, 3.2 and 4) as candidate resistance factors to be considered more broadly with respect to schistosome control efforts, including involving other Biomphalaria species vectoring S. mansoni in endemic areas in Africa.

Clusters of polymorphic transmembrane genes control resistance to schistosomes in snail vectors.

Schistosomiasis is a debilitating parasitic disease infecting hundreds of millions of people. Schistosomes use aquatic snails as intermediate hosts. A promising avenue for disease control involves leveraging innate host mechanisms to reduce snail vectorial capacity. In a genome-wide association study of Biomphalaria glabrata snails, we identify genomic region PTC2 which exhibits the largest known correlation with susceptibility to parasite infection (>15 fold effect). Using new genome assemblies with substantially higher contiguity than the Biomphalaria reference genome, we show that PTC2 haplotypes are exceptionally divergent in structure and sequence. This variation includes multi-kilobase indels containing entire genes, and orthologs for which most amino acid residues are polymorphic. RNA-Seq annotation reveals that most of these genes encode single-pass transmembrane proteins, as seen in another resistance region in the same species. Such groups of hyperdiverse snail proteins may mediate host-parasite interaction at the cell surface, offering promising targets for blocking the transmission of schistosomiasis.

Schistosomiasis is a widespread parasitic disease, affecting over 200 million people in tropical countries. It is caused by schistosome worms, which are carried by freshwater snails. These snails release worm larvae into the water, where they can infect humans ­ for example, after bathing or swimming. Treatment options for schistosomiasis are limited. Eliminating the freshwater snails is one way to control the disease, but this is not always effective in the long term and the chemicals used can also harm other animals in the water. Another way to manage schistosomiasis could be to stop the worms from infecting their snail host by breaking the parasites' life cycle without killing the snails. It is already known that some snails are naturally resistant to infection by some strains of schistosomes. Since this immunity is also inherited by the offspring of resistant snails, there is likely a genetic mechanism behind it. However, very little else is known about any genes that might be involved. Tennessen et al. therefore set out to identify what genes were responsible for schistosome resistance and how they worked. The experiments used a large laboratory colony of snails, whose susceptibility to schistosome infection varied among individual animals. To determine the genes behind this variation, Tennessen et al. first searched for areas of DNA that also differed between the immune and infected snails. Comparing genetic sequences across over 1,000 snails revealed a distinct region of DNA that had a large effect on how likely they were to be infected. This section of DNA turned out to be highly diverse, with different snails carrying varying numbers and different forms of the genes within this region. Many of these genes appear to encode proteins found on the surface of snail cells, which could affect whether snails and worms can recognize each other when they come into contact. This in turn could determine whether or not the worms can infect their hosts. These results shed new light on how the snails that carry schistosomes may be able to resist infections. In the future, this knowledge could be key to controlling schistosomiasis, either by releasing genetically engineered, immune snails into the wild (thus making it harder for the parasites to reproduce) or by using the snails' mechanism of resistance to design better drug therapies.

Heat shock increases hydrogen peroxide release from circulating hemocytes of the snail Biomphalaria glabrata.

Planorbid freshwater snails are important intermediate hosts for parasitic diseases caused by parasitic worms, most notably schistosomiasis. There are numerous reports of snails, specifically Biomphalaria glabrata, having compromised defences against schistosomes after being exposed to thermal stress. Environmental modifications to the defenses of schistosome transmitting snails could have negative ramifications for human disease risk in the context of climate change. Here the effects of heat shock on the production of hydrogen peroxide, a primary anti-microbial effector in many molluscs, were examined. The present findings show that heat shock increases NADPH oxidase 2 mRNA levels and hydrogen peroxide produced by snail hemocytes, and that both of these phenotypes could be reversed by an HSP-90 inhibitor. These findings indicate that snail defense systems are altered by heat shock at a molecular level in B. glabrata, and that snail immunity to many pathogens may be altered by the rapid variations in temperature that are associated with global climate change.

Glabralysins, Potential New ß-Pore-Forming Toxin Family Members from the Schistosomiasis Vector Snail Biomphalaria glabrata.

Biomphalaria glabrata is a freshwater Planorbidae snail. In its environment, this mollusk faces numerous microorganisms or pathogens, and has developed sophisticated innate immune mechanisms to survive. The mechanisms of recognition are quite well understood in Biomphalaria glabrata, but immune effectors have been seldom described. In this study, we analyzed a new family of potential immune effectors and characterized five new genes that were named Glabralysins. The five Glabralysin genes showed different genomic structures and the high degree of amino acid identity between the Glabralysins, and the presence of the conserved ETX/MTX2 domain, support the hypothesis that they are pore-forming toxins. In addition, tertiary structure prediction confirms that they are structurally related to a subset of Cry toxins from Bacillus thuringiensis, including Cry23, Cry45, and Cry51. Finally, we investigated their gene expression profiles in snail tissues and demonstrated a mosaic transcription. We highlight the specificity in Glabralysin expression following immune stimulation with bacteria, yeast or trematode parasites. Interestingly, one Glabralysin was found to be expressed in immune-specialized hemocytes, and two others were induced following parasite exposure.

Coordination of humoral immune factors dictates compatibility between Schistosoma mansoni and Biomphalaria glabrata.

Immune factors in snails of the genus Biomphalaria are critical for combating Schistosoma mansoni, the predominant cause of human intestinal schistosomiasis. Independently, many of these factors play an important role in, but do not fully define, the compatibility between the model snail B. glabrata, and S. mansoni. Here, we demonstrate association between four previously characterized humoral immune molecules; BgFREP3, BgTEP1, BgFREP2 and Biomphalysin. We also identify unique immune determinants in the plasma of S. mansoni-resistant B. glabrata that associate with the incompatible phenotype. These factors coordinate to initiate haemocyte-mediated destruction of S. mansoni sporocysts via production of reactive oxygen species. The inclusion of BgFREP2 in a BgFREP3-initiated complex that also includes BgTEP1 almost completely explains resistance to S. mansoni in this model. Our study unifies many independent lines of investigation to provide a more comprehensive understanding of the snail immune system in the context of infection by this important human parasite.

Investigation of defense response and immune priming in Biomphalaria glabrata and Biomphalaria straminea, two species with different susceptibility to Schistosoma mansoni.

For many years, the immune response of invertebrates was considered to lack any mechanism of memory. However, the study of their response has shown a kind of acquired immunity, which is not so well understood given the lack of knowledge of the invertebrate defense system. This event can be called "innate immune memory." Recent studies using Biomphalaria glabrata snails have reported this phenomenon, relating it to an increase in humoral products, but no focus was given to hemocyte response or to other species of snails. In this study, we focus on hemocyte dynamics and some humoral factors in the species B. glabrata and B. straminea, the most widespread species in Brazil, sensitized and non-sensitized to the Schistosoma mansoni worm. We report a change in the prevalent hemocyte type after sensitization, through an increase in the proportion of granulocytes, as well as a change in the total number of hemocytes caused by a second exposure to the parasite. We also showed that melanization is not a key factor in Biomphalaria snail defense and varies little after the second exposure event. The data reported in this article confirm the effect of immune priming on these snails and suggest that the increase of humoral products shown in the literature is accompanied by variation in hemocytes after sensitization.

Biomphalaria glabrata immunity: Post-genome advances.

The freshwater snail, Biomphalaria glabrata, is an important intermediate host in the life cycle for the human parasite Schistosoma mansoni, the causative agent of schistosomiasis. Current treatment and prevention strategies have not led to a significant decrease in disease transmission. However, the genome of B. glabrata was recently sequenced to provide additional resources to further our understanding of snail biology. This review presents an overview of recently published, post-genome studies related to the topic of snail immunity. Many of these reports expand on findings originated from the genome characterization. These novel studies include a complementary gene linkage map, analysis of the genome of the B. glabrata embryonic (Bge) cell line, as well as transcriptomic and proteomic studies looking at snail-parasite interactions and innate immune memory responses towards schistosomes. Also included are biochemical investigations on snail pheromones, neuropeptides, and attractants, as well as studies investigating the frontiers of molluscan epigenetics and cell signaling were also included. Findings support the current hypotheses on snail-parasite strain compatibility, and that snail host resistance to schistosome infection is dependent not only on genetics and expression, but on the ability to form multimeric molecular complexes in a timely and tissue-specific manner. The relevance of cell immunity is reinforced, while the importance of humoral factors, especially for secondary infections, is supported. Overall, these studies reflect an improved understanding on the diversity, specificity, and complexity of molluscan immune systems.

Proteomic, metabolic and immunological changes in Biomphalaria glabrata infected with Schistosoma mansoni.

Mansonic schistosomiasis is a neglected disease transmitted by Biomphalaria spp. snails. Understanding what happens inside the intermediate host is important to develop more efficient ways of reducing schistosomiasis prevalence. Our purpose was to characterize metabolic and immunological changes in Biomphalaria glabrata 24 h after exposure to Schistosoma mansoni. For this purpose, proteins were extracted from snails' whole tissue with Tris-Urea buffer and digested with tripsin. Mass spectrometry was performed and analyzed with MaxQuant and Perseus software. Also, the hemolymph of five snails 24 h post exposure was collected, and the numbers of hemocytes, levels of urea, uric acid, nitric oxide, calcium, glycogen and alanine and aspartate aminotransferases activities were assessed. Snails were also dissected for measurement of glycogen content in the cephalopodal region and gonoda-digestive gland complex. Globin domain proteins were found to be up-regulated; also the number of circulating hemocytes was significantly higher after 24 h of exposure to the parasite. NO levels were higher 24 h post exposure. Several proteins associated with energy metabolism were found to be up-regulated. Glycogen analysis showed a significant decrease in the gonad-digestive gland complex glycogen content. We found several proteins which seem to be associated with the host immune response, most of which were up-regulated, however some were down-regulated, which may represent an important clue in understanding B. glabrata - S. mansoni compatibility.

Comparison of NMRI Schistosoma mansoni Infection in Three Susceptible Laboratory Albino Strains of Biomphalaria glabrata.

Albino strains of Biomphalaria glabrata that are compatible with Schistosoma mansoni are commonly used to investigate snail-schistosome interactions, but whether they are all equally compatible is not known. In this study, compatibility with the Naval Medical Research Institute (NMRI) strain of S. mansoni was compared among 3 widely used albino strains: NMRI (the normal laboratory host for NMRI S. mansoni), M line, and University of Massachusetts Lowell (UML). Compatibility was assessed on the basis of infection prevalence following exposure to miracidia, the histological fate of sporocysts, and mitotic response in the snail amebocyte-producing organ (APO), a component of the internal defense system (IDS). Infection prevalence in UML was nearly identical to that in NMRI but was significantly lower in M line. Although the APO of UML showed no response to infection over the course of 9 days, mitotic activity was elevated in the APO of NMRI and M line, with that in M line being higher and more prolonged than in the APO of resistant BS-90 snails. Finally, hemocyte responses against some small primary sporocysts occurred at 1 and 3 days post-exposure (DPE) in all 3 strains, but in 2 of 5 M line a response also occurred against large primary sporocysts at 6 DPE. Thus, based on infection prevalence and tissue responses, compatibility with NMRI S. mansoni is lowest in M line, whereas UML and NMRI show the same degree of compatibility, despite decades of maintenance of this parasite strain in NMRI snails. The elevated mitotic response in the APO of M line and NMRI snails suggests that a response of the IDS can occur even in a compatible host-parasite relationship.

Allelic variation in a single genomic region alters the hemolymph proteome in the snail Biomphalaria glabrata.

Freshwater snails are obligate intermediate hosts for numerous parasitic trematodes, most notably schistosomes. Schistosomiasis is a devastating human and veterinary illness, which is primarily controlled by limiting the transmission of these parasites from their intermediate snail hosts. Understanding how this transmission occurs, as well as the basic immunobiology of these snails may be important for controlling this disease in the future. Allelic variation in the Guadeloupe resistance complex (GRC) of Biomphalaria glabrata partially determines their susceptibility to parasitic infection, and can influence the microbiome diversity and microbial defenses in the hemolymph of these snails. In the present study, we examine the most abundant proteins present in the hemolymph of snails that are resistant or susceptible to schistosomes, as determined by their GRC genotype. Using proteomic analysis, we found that snails with different GRC genotypes have differentially abundant hemolymph proteins that are not explained by differences in transcription. There are 13 revealed hemolymph proteins that differ significantly between resistant and susceptible genotypes, nearly 40% of which are involved in immune responses. These findings build on the mounting evidence that genes in the GRC region have multiple physiological roles, and likely contribute more extensively to the general immune response than previously believed. These data also raise the intriguing possibility that the GRC region controls resistance to schistosomes, not directly, but indirectly via its effects on the snail's proteome and potentially its microbiome.

Sympatric versus allopatric evolutionary contexts shape differential immune response in Biomphalaria / Schistosoma interaction.

Selective pressures between hosts and their parasites can result in reciprocal evolution or adaptation of specific life history traits. Local adaptation of resident hosts and parasites should lead to increase parasite infectivity/virulence (higher compatibility) when infecting hosts from the same location (in sympatry) than from a foreign location (in allopatry). Analysis of geographic variations in compatibility phenotypes is the most common proxy used to infer local adaptation. However, in some cases, allopatric host-parasite systems demonstrate similar or greater compatibility than in sympatry. In such cases, the potential for local adaptation remains unclear. Here, we study the interaction between Schistosoma and its vector snail Biomphalaria in which such discrepancy in local versus foreign compatibility phenotype has been reported. Herein, we aim at bridging this gap of knowledge by comparing life history traits (immune cellular response, host mortality, and parasite growth) and molecular responses in highly compatible sympatric and allopatric Schistosoma/Biomphalaria interactions originating from different geographic localities (Brazil, Venezuela and Burundi). We found that despite displaying similar prevalence phenotypes, sympatric schistosomes triggered a rapid immune suppression (dual-RNAseq analyses) in the snails within 24h post infection, whereas infection by allopatric schistosomes (regardless of the species) was associated with immune cell proliferation and triggered a non-specific generalized immune response after 96h. We observed that, sympatric schistosomes grow more rapidly. Finally, we identify miRNAs differentially expressed by Schistosoma mansoni that target host immune genes and could be responsible for hijacking the host immune response during the sympatric interaction. We show that despite having similar prevalence phenotypes, sympatric and allopatric snail-Schistosoma interactions displayed strong differences in their immunobiological molecular dialogue. Understanding the mechanisms allowing parasites to adapt rapidly and efficiently to new hosts is critical to control disease emergence and risks of Schistosomiasis outbreaks.

Changes in hemocytes of Biomphalaria glabrata infected with Echinostoma paraensei and exposed to glyphosate-based herbicide.

The immune system of snails is highly sensitive to pollutants, which can suppress its immune response. We investigated the effects of exposure to the glyphosate-based herbicide Roundup® Original on the snail Biomphalaria glabrata infected by the platyhelminth Echinostoma paraensei by evaluating changes in the snail's internal defense system. Four cohorts were studied: control group, infected snails, snails treated with Roundup®, and snails infected and treated with Roundup®. The hemocyte viability was assessed, morphological differentiation of cells was observed and flow cytometry was performed to determine the morphology, viability and the lectin expression profiles. The frequencies of dead hemocytes were lower in the infected group and higher in both pesticide treated groups. Three cell types were identified: blast-like cells, hyalinocytes and granulocytes. The highest number of all types of hemocytes, as well as the highest number of dead cells, were observed in the infected, pesticide-treated group. The association between infection and herbicide exposure greatly increased the frequency of dead hemocytes, suggesting that this condition impairs the internal defense system of B. glabrata making the snails more vulnerable to parasitic infections.

Molecular characterisation of immunological memory following homologous or heterologous challenges in the schistosomiasis vector snail, Biomphalaria glabrata.

Invertebrate immune response may be primed by a current infection in a sustained manner, leading to the failure of a secondary infection with the same pathogen. The present study focuses on the Schistosomiasis vector snail Biomphalaria glabrata, in which a specific genotype-dependent immunological memory was demonstrated as a shift from a cellular to a humoral immune response. Herein, we investigate the complex molecular bases associated with this genotype-dependant immunological memory response. We demonstrate that Biomphalaria regulates a polymorphic set of immune recognition molecules and immune effector repertoires to respond to different strains of Schistosoma parasites. These results suggest a combinatorial usage of pathogen recognition receptors (PRRs) that distinguish different strains of parasites during the acquisition of immunological memory. Immunizations also show that snails become resistant after exposure to parasite extracts. Hemolymph transfer and a label-free proteomic analysis proved that circulating hemolymph compounds can be produced and released to more efficiently kill the newly encountered parasite of the same genetic lineage.

Proteomic Analysis of Biomphalaria glabrata Hemocytes During in vitro Encapsulation of Schistosoma mansoni Sporocysts.

Circulating hemocytes of the snail Biomphalaria glabrata, a major intermediate host for the blood fluke Schistosoma mansoni, represent the primary immune effector cells comprising the host's internal defense system. Within hours of miracidial entry into resistant B. glabrata strains, hemocytes infiltrate around developing sporocysts forming multi-layered cellular capsules that results in larval death, typically within 24-48 h post-infection. Using an in vitro model of hemocyte-sporocyst encapsulation that recapitulates in vivo events, we conducted a comparative proteomic analysis on the responses of hemocytes from inbred B. glabrata strains during the encapsulation of S. mansoni primary sporocysts. This was accomplished by a combination of Laser-capture microdissection (LCM) to isolate sections of hemocyte capsules both in the presence and absence of sporocysts, in conjunction with mass spectrometric analyses to establish protein expression profiles. Comparison of susceptible NMRI snail hemocytes in the presence and absence of sporocysts revealed a dramatic downregulation of proteins in during larval encapsulation, especially those involved in protein/CHO metabolism, immune-related, redox and signaling pathways. One of 4 upregulated proteins was arginase, competitor of nitric oxide synthetase and inhibitor of larval-killing NO production. By contrast, when compared to control capsules, sporocyst-encapsulating hemocytes of resistant BS-90 B. glabrata exhibited a more balanced profile with enhanced expression of shared proteins involved in protein synthesis/processing, immunity, and redox, and unique expression of anti-microbial/anti-parasite proteins. A final comparison of NMRI and BS-90 host hemocyte responses to co-cultured sporocysts demonstrated a decrease or downregulation of 77% of shared proteins by NMRI cells during encapsulation compared to those of the BS-90 strain, including lipopolysaccharide-binding protein, thioredoxin reductase 1 and hemoglobins 1 and 2. Overall, using this in vitro model, results of our proteomic analyses demonstrate striking differences in proteins expressed by susceptible NMRI and resistant BS-90 snail hemocytes to S. mansoni sporocysts during active encapsulation, with NMRI hemocytes exhibiting extensive downregulation of protein expression and a lower level of constitutively expressed immune-relevant proteins (e.g., FREP2) compared to BS-90. Our data suggest that snail strain differences in hemocyte protein expression during the encapsulation process account for observed differences in their cytotoxic capacity to interact with and kill sporocysts.

Reversal of Schistosome Resistance In Biomphalaria glabrata By Heat Shock May Be Dependent On Snail Genotype.

Several genes have recently been shown to affect the innate resistance of laboratory strains of Biomphalaria glabrata to infection with Schistosoma mansoni, including Hsp90, the expression of which following a brief exposure to elevated temperature can interfere with resistance in juvenile BS-90 snails. Because a prior study failed to see a similar effect in adult snails, juvenile BS-90 snails were exposed to 10 or 50 miracidia following a 4.5 to 6 hr incubation at 33 or 37 C. Snails were then monitored for production of secondary sporocysts or release of cercariae. In addition, snails exposed to 33 C were examined histologically between 1 and 15 days post exposure (DPE) to 30 miracidia to assess the fate of primary sporocysts. Other than elevated numbers of viable primary sporocysts in the tissues of heat shocked snails at 3 DPE, no statistically significant effect of elevated temperature was observed. This discrepancy with regard to prior studies is hypothesized to result from genetic divergence in different laboratory colonies of the same strain of snail.

Allelic variation partially regulates galactose-dependent hydrogen peroxide release from circulating hemocytes of the snail Biomphalaria glabrata.

Freshwater snails are the intermediate hosts for numerous parasitic worms that are detrimental to human and agricultural health. Understanding the immune responses of these snails could be vital for finding ways to block transmission of those parasites. Allelic variation in a recently discovered genomic region in the snail, Biomphalaria glabrata, influences their susceptibility to schistosomes. Here we tested whether genes in that region, termed the Guadeloupe Resistance Complex (GRC), are involved in recognition of common pathogen-associated molecules that have been shown to be stimulants of the hydrogen peroxide defense pathway. We show that hemocytes extracted from individuals with one of the three GRC genotypes released less hydrogen peroxide than the other two genotypes, after stimulation with galactose. This difference was not observed after stimulation with several other microbial-associated carbohydrates, despite those ligands sharing the same putative pathway for hydrogen peroxide release. Therefore, we conclude that allelic variation in the GRC region may influence the recognition of galactose, rather than the conserved downstream steps in the hydrogen peroxide pathway. These results thus are consistent with the hypothesis that proteins produced by this region are involved in pathogen recognition.

Schistosomiasis from a Snail's Perspective: Advances in Snail Immunity.

The snail's immune response is an important determinant of schistosome infection success, acting in concert with host, parasite, and environmental factors. Coordinated by haemocytes and humoral factors, it possesses immunological hallmarks such as pattern recognition receptors, and predicted gastropod-unique factors like the immunoglobulin superfamily domain-containing fibrinogen-related proteins. Investigations into mechanisms that underpin snail-schistosome compatibility have advanced quickly, contributing functional insight to many observational studies. While the snail's immune response is important to continue studying from the perspective of evolutionary immunology, as the foundational determinants of snail-schistosome compatibility continue to be discovered, the possibility of exploiting the snail for schistosomiasis control moves closer into reach. Here, we review the current understanding of immune mechanisms that influence compatibility between Schistosoma mansoni and Biomphalaria glabrata.

Whole genome analysis of a schistosomiasis-transmitting freshwater snail.

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.