Summarizing discussion
Development of parasitism
Parasitism is a relationship between two organisms in which one of them (the parasite) lives in or on the other (the host) and lives at the expense of that host. Life as a parasite offers advantages that surpass its inconveniences. The main advantage is the excess of nutrients. In addition, parasitism offers the possibility to lose genes encoding proteins that are essential under free-living conditions, but of which the function is taken over by the host. A parasite also benefits from the homeostasis of the host, giving the parasite a very constant environment to live in. However, living in or on a host organism also means living in constant threat of the host immune system. Another disadvantage is the more challenging way of reproduction, which is reflected in the numerous complex life cycles of parasites.
Parasitism has evolved independently many times during the history of life. Almost all free-living organisms are host to various parasitic taxa (139). There are parasites in nearly all ecosystems and there is substantial evidence that parasites shape host population dynamics, alter interspecific competition, influence energy flow and appear to be important drivers of biodiversity (86).
A parasite's way of living inevitably causes damage to its host, if not physical, than by taking up nutrients that would otherwise be for the host itself. Parasites generally die when their host does. Hence, parasites have evolved in such a way that the damage they cause will not kill their host, at least not before the parasites have reproduced. The harm caused by schistosomes is usually mild. They can cause anemia because they feed on blood, but also as a result of blood loss through the wounds made by the eggs when they pass the endothelium and gut wall. Schistosome infections can also lead to malnutrition. The eggs that do not exit the body, elicit an immune response that initially is not very harmful to the host but can be detrimental when it is at a critical location, e.g. the central nervous system (CNS), or after long lasting accumulation causing portal hypertension and which may lead to liver failure. Also, prolonged inflammation may contribute to the development of malignancies.
Parasites adapted to nearly every kind of tissue of the (human) body exist. Each parasite has evolved for optimal fitness within its niche. Schistosomes are blood-dwelling parasites. The worms have to overcome many challenges in order to get into the circulation, maintain themselves, reproduce and to excrete the eggs for survival of their species. They have developed a large armoury of interventions with their host to protect themselves and sometimes even to turn potential harmful host reactions in highly useful assistance for example in excretion of the eggs.
Parasitic helminths
Infection and migration
Penetration of the skin is a fairly common mode of entrance for parasitic worms. This can be achieved either by a vector injecting worm larvae or by skin penetration of the larval parasites themselves. Filaria worms are injected through the skin by flies or mosquitoes. Hookworm and Strongyloides larvae penetrate the skin by themselves, as do schistosome cercariae.
Tissue migration is a common feature in the life cycles of parasitic worms. Similar to schistosomula, both hookworm and Strongyloides larvae migrate to the lungs. However, while schistosomula further migrate via the liver to the portal vein to mate and mature, hookworm and Strongyloides larvae enter the alveoli, are coughed up and subsequently swallowed to reach their final location, which is the intestinal lumen where they mature and reproduce. And even Ascaris larvae, which enter the human host when eggs are ingested, need to penetrate the mucosa of the gut and migrate through the body in order to fully mature before homing in the intestinal lumen - where they have been before as eggs. Thus, although tissue invasion and migration appears as a redundantly complicated step in the life cycle of parasitic worms, it is so widespread that it seems to provide essential developmental needs.
Tissue migration is referred to as larva migrans when it causes disease symptoms. As can be deduced from the life cycles of the helminths that cause larva migrans, symptoms are temporally and disappear once the adult worms have reached their niche. Only upon recurrent reinfection or in the case of Strongyloides, where auto-infection can occur, larva migrans can last for longer periods. Tissue migration of schistosomes doesn't usually cause symptoms, even though it elicits a remarkable immune response.
Although very common, not all parasitic worms migrate through tissues. Enterobius and Trichuris are both ingested as eggs and hatch and develop to adult worms within the gut. And also for the flatworms Opisthorchis viverrini, Clonorchis sinensis and Dicrocoelium dendriticum the only organ system they encounter from their host, is the intestinal tract and the bile duct.
On the other hand, not all ingested parasitic worms home in the intestinal tract. Some are ingested as eggs or as larvae and migrate to other tissues to mature and reproduce. Dracunculus are ingested with their intermediate hosts, copepods, in drinking water. Larvae, released from the copepods which die in the stomach, penetrate the host stomach and intestinal wall to mature and copulate in the abdominal cavity and retroperitoneal space. The female worms then migrate to the subcutaneous tissues towards the skin surface where larvae are released through a skin blister. Also Trichinella and Echinococcus are parasitic worms that infect humans through ingestion. They then migrate throughout the body where cysts are formed, which only infect the next host through carnivorism, when ingested with the current host as a meal for the new host.
Exit of progeny
In order to replicate, the progeny of parasitic worms needs a way to exit the host and infect another host. The majority of human parasitic worms spreads through eggs or larval stages that leave their host. For intestinal parasites, the route of exit is obvious. No complex mechanisms need to be adopted as eggs or larvae, which do not attach to the gut wall, will automatically be excreted following peristaltic bowel movements and defecation. Schistosoma mansoni also uses this mechanism, but first has to overcome some barriers to get their progeny into the gut. As oviposition occurs in the veins, eggs have to pass the endothelial wall and the gut wall. As for intestinal worms, the exit of eggs is with the feces. Miracidia, schistosome larvae, hatch from the eggs immediately when they come into fresh water. Time to infect the intermediate host, an aquatic snail, is then limited. Some parasitic worms, such as Fasciola, Ascaris and Echinococcus have very resistant eggs or cysts which can stay viable in the environment for a long time. Hatching occurs when favourable conditions are met, followed by infection of the next (intermediate) host.
Free-living stages of parasitic worms are usually non-feeding and thus are either encysted such as the metacercariae of Fasciola spp., or have a restricted time frame to infect the next host. The latter is the case for schistosomes, where both the miracidia infecting the snail and the cercariae infecting the mammalian host have a glycogen reserve for about 12-24 hours (89,182,202). Hookworm and Strongyloides have free-living stages that feed on soil bacteria (rhabditiform larvae). When transformed into non-feeding, infective filariform larvae they encounter the same time challenge of finding a suitable host as do schistosomes. Strongyloides eggs hatch within the uterus of the female worm. As transformation into infectious filariform larvae takes less then two days, this can occur within the host, before the larvae are excreted. The larvae can reinfect the host, which is referred to as auto-infection. In severely immunocompromized hosts, aberrant auto-infection may lead to hyperinfection syndrome. Strongyloides also have a free-living cycle, where rhabditiform larvae mature into reproductive male and female worms.
As mentioned above, intestinal parasites have an easy exit. Tissue-dwelling parasitic worms on the other hand need to be more inventive to exit and spread. Carnivorism is a well proven concept for life cycle continuation, used for example by some tapeworms (Taenia solium, Echinococcus) and Trichinella. Filaria larvae, microfilaria, circulate within the bloodstream and are aspirated and further spread to their new host by the fly or mosquito vector upon feeding. Microfilariae from tissue-dwelling filariae generally hatch in the uterus of female worms, while for blood-dwelling species microfilariae remain sheathed in the envelope of the egg and will exsheath within the intermediate host. Dracunculus worms do not lay eggs, but produce live larvae. These leave the host through a sore blister in the skin, usually the foot, which is immersed in water to ease the pain.
Toxocara is an intestinal parasitic worm in dogs and cats. Similar to many intestinal parasites, eggs leave with the feces. Worms can mature and reproduce in young dogs. However, in infected adult dogs, Toxocara development is hampered. But the infection can be transferred transplacental, which means that an infected pregnant dog can infect her unborn pups in utero. In addition, an infected bitch can infect her newborns though milk. Toxocara development is then resumed in young dogs.
Feeding habits
Most parasitic worms that infect humans feed on tissue, blood or other body fluids, even when residing in the intestinal tract. In that respect, schistosome worms have chosen a very pleasant location where food literally drifts by. All they need to do in order to get fed, is sit and open their mouth or absorb through their tegument. And that is exactly what they do. Female schistosome worms feed largely on circulating red blood cells. Males mainly absorb nutrients through their tegument. Tissue-dwelling worms generally feed on the tissue and body fluids they live in. Some of them eventually encyst and go into dormant stages and spread through carnivorism. Hookworms and Strongyloides, both intestinal worms, hook themselves to the mucosa to feed on blood and epithelial cells. Where hookworms just hook themselves in the mucosa, Trichuris worms dig in half their body, while the other half of their body hangs freely in the gut lumen.
Some intestinal worms do not feed on human tissue but feed on the predigested intestinal liquid content. Among them are Ascaris, Toxocara and tapeworms. The latter have no mouth and absorb all the nutrients through their tegument, which is covered by microvilli to increase surface area.
Whichever locations parasitic worms chose, they generally have plenty of food surrounding them as they typically feed on the host. This allows them to use an inefficient energy metabolism in which substrates are not fully oxidized.
Host defence
The components of the immune system of the host are a continuous threat to the parasites living in the host. In that respect, the choice for the circulation as a habitat of schistosomes is remarkable, as this is the body compartment where all immune components are constantly present: immune cells, including T-cells, eosinophils and macrophages and other immune components such as complement, cytokines and chemokines. The presence of the immune effectors is much lower in the tissues and even lower in the gut. However, as parasitic worms are large compared to the immune cells, there is not much these immune cells can do to them even with help of other components of the immune system. Besides, many tissue-dwelling parasitic worms have developed effective immune evading strategies. Sometimes the immune activation results in encapsulation of the parasite (larvae), as is the case with larvae of species that infect through carnivorism such as the cyst stage of Echinococcus and Taenia solium and with schistosome eggs that are trapped in the body.
On schistosome eggs and worms
Eggs and worms of schistosomes have opposite interests, namely get out of the host versus stay in the host. Thus egg-host interactions and worm-host interactions have to be different.Schistosome worms have evolved to produce a large progeny in order to maximize the probability of species survival. The adult worms do not look after their offspring once the eggs are laid. Eggs have to get out of the host on their own, even though they are incapable of moving by themselves and the way out is a difficult one. Eggs have to penetrate tissues in order to get to the gut lumen (urine bladder in the case of S. haematobium) where they are subsequently released in the environment together with the feces (or urine).
Egg-host interactions
An egg is defined as an animal reproductive body consisting of an ovum/female gamete together with its nutrient material and a protective covering and, when fertilized, having the capacity to develop into a new individual capable of independent existence.
Schistosome eggs are build of a fertilized oocyte surrounded by vitelline cells containing nutrients and material for the eggshell (175). By the time the egg leaves the mammalian host, the fertilized oocyte has developed into a fully matured miracidium covered by a tanned protein eggshell. Once the egg is released in the water, osmotic changes result in swelling of the internal material thereby increasing the internal pressure on the eggshell. This leads to hatching of the miracidium from the egg.
Formation of the eggshell
A major function of the eggshell is to restrict the permeability of the egg and maintain a certain environment within the egg for embryonic development and survival (196). Eggshells of trematodes are made of proteins which are cross-linked by tyrosinase activity forming quinone bonds. This eggshell of tanned proteins has underlying layers and envelopes. The subshell cellular layer of schistosome eggs is named von Lichtenberg's envelope. A non-cellular layer, Reynolds' layer, is situated between von Lichtenberg's envelope and the eggshell (6,123). Schistosome eggshell formation starts in the ootype within the female, where ootype contraction leads to release of eggshell precursor proteins from the vitelline droplets. These form the eggshell upon quinone tanning. Specific eggshell precursor proteins have first been described in the late 80s and early 90s (13,14,33,93,94,150,169). As the eggshell is a direct site of interaction between the egg and the host, its composition is of major importance in host-parasite interaction. Results of mass spectrometry, immunohistochemical and amino acid analysis of the protein composition of the eggshell are described in chapter 2. The experiments revealed that the major component of the eggshell is the putative eggshell protein p14. This protein has characteristic short repeat sequences of which nearly half of the amino acid residues are glycines. High glycine content is a general feature of trematode eggshell proteins and has also been described for Fasciola hepatica, Opisthorchis viverrini and Paragonimus westermani. Mass spectrometry analysis did not reveal the presence of p14 in eggshell, probably due to its high tyrosine content transformed in quinone bonds and due to high lysine levels leading to very short peptides after trypsin digestion. However, the presence of p14 was shown by immunoblot. In addition, amino acid analysis showed a glycine content of 36% in total hydrolyzed eggshell. This high glycine content is readily explained by a high contribution of p14 to total eggshell.
A wide range of schistosome proteins was detected by mass spectrometry in purified eggshell samples. This indicates that a variety of non-eggshell specific proteins is also incorporated in the eggshell. The majority of these proteins are generally abundant cellular proteins such as the major egg antigen p40, HSP70 and many glycolytic enzymes. These proteins are suggested to originate from surrounding vitelline cells and happened to be around at the site and time of eggshell synthesis. Hence, these non-eggshell specific proteins were coincidently cross-linked to the major eggshell proteins. The absence of the major egg secretion proteins IPSE/alpha-1 and omega-1 indicates that cross-linking is finished before the egg has fully matured and starts secreting. The absense of host plasma proteins in eggshell indicates that eggshell formation is finished even before oviposition.
Eggshell contribution to the journey of the S. mansoni egg
Most eggs of parasitic helminths are deposited in the gut. Their way out is straightforward and does not need exploited assistance of the host. In contrast, schistosome eggs exit the female body in the mesenteric capillary venules, close to the bowel. It takes at least a few days for a schistosome egg to exit the host, but it may take up to several weeks. The eggs need to get into the gut in order to get out of the host. However, blood flowing through the venules can easily carry the egg along, away from the bowel and heading towards the liver. To prevent this, eggs have to quickly adhere to the vessel wall. Previous experiments reported vast adhesion of platelets to eggshell (203). In addition, the experiments in chapter 4 showed that VWF also adheres to eggshell directly. Unfolded VWF can connect platelets to clotting factors and injured surfaces of the endothelium through many binding domains (105159) and plays an important role in platelet-vessel wall adhesion by binding both platelets and the extracellular matrix of the vessel wall containing collagen and fibrin. Furthermore, VWF plays a role in platelet cross-linking and platelet plug expansion (105). By bridging between the eggshell and the extracellular matrix, VWF may attach the eggshell to the endothelium. In addition, VWF can contribute to eggshell adhesion to endothelium indirectly as VWF in combination with platelets can induce platelet adhesion, platelet activation and secondary hemostasis, allowing the formation of a stable clot. This is in accordance with the findings of Ngaiza and Doenhoff (1990) (125) who previously demonstrated that platelets play a role in egg extravasation.
Binding of fibrinogen and fibronectin to eggshell was also demonstrated. Where fibrin, the cleaved product of fibrinogen, is the main component of a blood clot, fibronectin plays an essential role in cell adhesion and wound healing. Thus, both can play an important role in egg adhesion to the endothelium. Enolase was previously identified in eggshell. Its presence there seems accidental. Enolase has been described to bind host fibronectin in bacterial pathogens (57). This could also be the case in S. mansoni eggshell, where enolase-binding fibronectin can further enhance endothelium binding of eggshell. Chapter 4 reports that fibronectin was one of the main plasma proteins that bound to eggshell and the major one in the high molecular weight range. No tests were performed to determine whether enolase was the major fibronectin-binding eggshell protein.
Next to fibronectin, enolase can bind plasminogen (8,43,141,206). Plasminogen is the precursor of plasmin, a serine protease that cleaves fibrin and VWF. Small amounts of plasminogen may facilitate fibrinolysis of the clot surrounding the eggs after extravasation. However, in the mass spectrometry experiments plasminogen was not elevated in plasma proteins that bound to eggshell compared to full plasma. This does not exclude that plasminogen is bound to eggshell. In fact, small amounts of plasmin are probably needed to prevent the excessive expansion of the clot leading to occlusion of the vessel.
Platelet activation and blood coagulation around schistosome eggs can further be enhanced by shear stress and turbulence within the vessel (177). Both can be caused by mechanical obstruction by worms and eggs. By their presence and as a result of their adherence to the vessel wall, schistosome worms also cause damage to the endothelium, which in itself is another strong activator of platelets and blood coagulation and of endothelial cells (168). Eggs of both S. mansoni and S. haematobium can induce endothelial cell proliferation in vitro (55,67). In vitro, endothelial cells overgrow schistosome eggs within a few hours after oviposition (64). Thus, eggs can passively cross the endothelium by the non-specific response of endothelial cells. File (1995) (64) also showed that eggs deposited directly by adult worms elicited a more rapid and complete response than embryonated eggs isolated from the liver tissues.
In short, schistosome eggs can probably passively pass the endothelium after binding it. Binding of the eggshell is facilitated by the composition of the eggshell (chapter 2 and 3) which binds platelets and plasma proteins involved in coagulation (chapter 4).
The next step is to cross the tissue of the gut wall and get excreted with the feces. The mechanism of this process are largely unknown, but it is likely to depend on the host immune system (see below).
Eggshell interaction with the immune system
Most eggs of parasitic helminths are deposited in the gut and have little interaction with the immune system. In contrast, schistosome eggs are in constant interaction with the host from the moment of oviposition until they have reached the intestinal lumen. Half of the eggs does not succeed to exit the blood vessel. They are dragged along with the blood stream and get stuck in small vessels. Eggs elicit a strong immune response and those stuck in the host tissues hence induce granuloma formation.
While schistosome adult worms must prevent an effective immune response, eggs need the immune system in order to be excreted (49). The schistosome eggshell and egg secretions contain many immunogenic proteins and glycans (30,40,110,149) (chapter 2). These immunogenic components of eggshell and egg secretions may be of major interest in the scope of immune mediated egg excretion. Eggshells and egg secretions induce a Th2 response via IL-4 activated macrophages and CD4+ T-lymphocytes. Fecal excretion of eggs is immune mediated and egg excretion rate and CD4+ T-cell percentage are positively correlated (49,90). Both major egg secretion products IPSE/alpha-1 and Omega-1 alone are capable of Th2 skewing (59,163,164,178), but secretion of these glycoproteins only starts a few days after oviposition when the egg has matured. Because maturation takes about a week, T-cells are likely to play a role during penetration through the gut wall, when the eggs have already adhered to and passed through the endothelium.
The schistosome eggshell contains more than specific eggshell proteins alone. The observed incorporation of these other proteins as reported in chapter 2, probably originate from neighbouring vitelline cells. This may appear as an unspecific feature of eggshell production. But many of the proteins identified to be part of the eggshell are known schistosome antigens, such as p40, phosphoenolpyruvate carboxykinase (PEPCK) and thioredoxin peroxidase. These proteins induce cellular immune responses (3,200) or antibody responses (122). They may hence prime the immune system and contribute to the penetration of the eggs through host tissues.
However useful the immune response may be for extravasation, immune activation has a hindside. The main cause of pathology in schistosomiasis are the non-excreted eggs which are trapped in the host tissue, generally the liver. Trapped eggs are enveloped in granulomas which are composed of eosinophils, CD4+ T-lymphocytes, macrophages and collagen fibres. It is the Th2 response generated by the host against antigens secreted by the parasite eggs that is responsible for the granuloma formation (137). In absence of the Th2 response, granulomas are not formed and continuous production of egg secretion products leads to severe immunopathology and hepatotoxic liver damage. In experimentally infected mice, this rapidly leads to death of the mice. Granulomas isolate the eggs and prevent the further spread of egg secretions. As the eggs die, the granulomas resolve, leaving fibrotic plaques. Accumulation of eggs and hence granulomas can eventually lead to permanent fibrotic changes in the liver, liver damage and portal hypertension.
In addition to the findings that eggshell contains a range of proteins known to be immunogenic, chapter 3 shows that immune sera contain antibodies which react with the eggshell. The formed antigen-antibody complex can induce chronic inflammatory responses where the interaction between CD4+ T-cells, macrophages and cytokines can cause granulomas to form (201).
Next to proteins, eggshell contains glycans. Schistosome glycans are the major inducers of the immune response (188) and the synthetic glycans GalNAc-4GlcNAc (LacdiNAc, LDN) and Gal1-4GlcNAc (LacNAc, LN) alone can induce granulomas (185).
Both eggshells and egg secretions induce antibody responses, as do adult worms. There is some overlap between worm and egg antigens, but there are enough differences to employ them usefully for diagnostics. That is described in chapter 5, where the differences in antibody responses to eggs and worms are used to differentiate between neuroschistosomiasis and other causes of transverse myelitis. It is essential to be certain of the diagnosis neuroschistosomiasis, before the start of therapy that includes immunosuppressive corticosteroids. These are contra-indicated in case of viral or bacterial causes of transverse myelitis. The key feature of the proposed test is to discriminate between antibodies in the cerebrospinal fluid (CSF) produced in situ and leakage of antibodies from blood plasma into the CSF due to damage to the blood-brain-barrier. The former indicates the presence of schistosome antigens in the CNS, while the latter points to another cause of the transverse myelitis. As neuroschistosomiasis is a result of nerve compression due to inflammation around schistosome eggs deposited near the nerves, the hypothesis is that anti-egg IgG, when normalized to anti-worm IgG, would be enriched in the CSF compared to the blood. Two schistosome-positive patients with transverse myelitis with an infectious cause for which no other pathogen was identified, had a positive test result, i.e. had a ratio ≥2. The egg-worm antibody index appears to be a valuable tool in the confirmation of neuroschistosomiasis. Further validation of this ratio is required in a larger group of patients, both travelers and patients in schistosome-endemic areas. It is important to distinguish these two groups of patients, as in endemic regions antibody levels may drop below cut-off values in chronic or recurrent infections.
Worm-host interactions
Many parasitic worms travel through host tissues at some point in their life cycle. They are then in constant interaction with the host immune system and have to prevent a damaging immune response. The outer surface of the worms is a major site of host-parasite interaction. It protects the worms and has other functions involved in immune invasion, excretion of proteins and uptake of nutrients.
The surface of blood-dwelling trematodes is the tegument. It consists of two lipid bilayers that overlay the syncytium. It forms a large surface made of lipids, glycans and proteins which can be detected by the immune system. In addition, (immunomodulatory) schistosome proteins are secreted through the tegument.
The protein composition of the tegument has been studied extensively (15,16,17,184). These tegumental proteins consist of membrane proteins, cytoskeleton proteins, proteins and secreted proteins. There is also a number of proteins unique to schistosomes that were specifically detected in the tegument (184).
Lipids form a major component in tegument, which contains high amounts of cholesterol, sphingomyelin and saturated (ether-linked) phospholipid species (2,151). The most abundant phospholipid classes in membranes of schistosomes are phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The diacyl-phospholipid species composition has been characterized for these phospholipid classes and this revealed that the species composition of these phospholipids is tegument-specific and differs from that of whole worm (21). In chapter 6 an analysis of the species composition of all major phospholipid classes is given, including phosphatidylinositol (PI), phosphatidylserine (PS) and lysophosphopolipids in isolated tegumental membranes. For most phospholipid classes, the species composition is substantially different in the tegument compared to whole worms. This is true for the PC and PS species. In contrast, diacyl-phospholipid species composition is strikingly similar for PI species. Furthermore, the tegument membranes were specifically enriched in lysophospholipids, especially lysophosphatidylserine (lyso-PS) and lysophosphatidylethanolamine (lyso-PE). In addition, the tegument was enriched in eicosaenoic acid (20:1) containing lysophospholipids in the phospholipid classes PS and PE, but not in PC and PI.
Lysophospholipids are minor compounds in membranes, but they play an important role in signal transduction. They also play a role in host-parasite interactions. It has been described that schistosome lysophosphatidylcholine (lyso-PC) can lead to lysis of red blood cells and cause immobilization of membrane components of red blood cells (71). Lyso-PS species have been shown to activate TLR2 on host immune cells and induce the development of IL-10 producing regulatory T-cells (187). Hence schistosome lyso-PS from the tegument may down regulate the immune response. Althought tegument appeared to be specifically enriched in lyso-PS, no lyso-PS could be detected as a secreted phospholipid in incubation medium or in host plasma (chapter 6). Circulating amounts are thus below detection level. This may be because lysophospholipids do not bind to albumin. Due to their amphipathic nature, lysophospholipids readily incorporate into membranes. This is especially true for schistosome lysophospholipids with long chain fatty acids that are relatively hydrophobic. In vitro, no acceptor membrane is available for excreted lysophospholipids. Hence, lysophospholipids possibly reincorporate into the tegumental membranes as the only available phospholipid membranes. In vivo, the acceptor membranes could be those of endothelial cells or those from circulating cells. While no free circulating (tegument specific) lyso-PS could be detected in plasma, it may still be excreted and immediately come in contact with the effector cells of the immune system and activate them to induce a regulatory immune response. Furthermore, incorporation of schistosome (lyso)phospholipids into membranes of host immune effector cells or endothelial cells may alter the biophysical properties of the membranes because of the structure of these unusual long and unsaturated fatty acids.
Phospholipid analysis in blood plasma revealed an interesting difference between phospholipid composition in blood plasma of infected hamsters and that of non-infected hamsters. Blood plasma of hamsters infected with schistosomes had substantially lower PI content. These host phospholipids have precursor functions in lipid signalling, cell signalling and membrane trafficking. Reduction of PI by schistosomes seems peculiar and there are no mechanisms known to contribute to this.
Unlike fatty acids, phospholipids do not bind albumin. PI in blood plasma are likely to constitute exosomes or microvesicles. Exosomes are released by activated cells of the immune system and are involved in intercellular communication to mediate the activation of the immune response (179). Reduction in PI may indicate that schistosomes alter the release of exosomes, which may affect the immune response.
Concluding remarks/future directives
Both schistosome worms and schistosome eggs are in constant interaction with their host. Worms and eggs have defined interactive surfaces which are highly unusual and specific in nature and composition. Further analysis of these structures could provide valuable information about the biology of schistosomes. Because these structures are so specific, they could serve as targets for vaccine and anti-schistosomal drug development.