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Seminars in Immunopathology Jun 2020Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other... (Review)
Review
Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other mammalian) water contact with surface water contaminated by faeces or urine, as well as specific freshwater snails acting as intermediate hosts. The main disease-causing species are S. haematobium, S. mansoni and S. japonicum. According to the World Health Organisation, over 250 million people are infected worldwide, leading to considerable morbidity and the estimated loss of 1.9 million disability-adjusted life years (DALYs), a likely underestimated figure. Schistosomiasis is characterised by focal epidemiology and an over-dispersed population distribution, with higher infection rates in children. Complex immune mechanisms lead to the slow acquisition of immune resistance, but innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is most evident in travellers following a primary infection. Chronic schistosomiasis affects mainly individuals with long-standing infections residing in poor rural areas. Immunopathological reactions against schistosome eggs trapped in host tissues lead to inflammatory and obstructive disease in the urinary system (S. haematobium) or intestinal disease, hepatosplenic inflammation and liver fibrosis (S. mansoni and S. japonicum). An effective drug-praziquantel-is available for treatment but, despite intensive efforts, no schistosomiasis vaccines have yet been accepted for public use. In this review, we briefly introduce the schistosome parasites and the immunopathogenic manifestations resulting from schistosomiasis. We then explore aspects of the immunology and host-parasite interplay in schistosome infections paying special attention to the current status of schistosomiasis vaccine development highlighting the advancement of a new controlled human challenge infection model for testing schistosomiasis vaccines.
Topics: Animals; Anthelmintics; Child; Humans; Schistosoma haematobium; Schistosoma mansoni; Schistosomiasis; Vaccines
PubMed: 32076812
DOI: 10.1007/s00281-020-00789-x -
Research in Veterinary Science Mar 2021Echinococcus spp. have a global distribution and are found on every continent except Antarctica. Infections with these parasites are considered extremely serious,... (Review)
Review
Echinococcus spp. have a global distribution and are found on every continent except Antarctica. Infections with these parasites are considered extremely serious, contributing to significant morbidity and mortality in addition to substantial economic losses to the livestock industry. Echinococcus granulosus sensu lato (s.l.) and Echinococcus multilocularis, causing cystic echinococcosis (CE) and alveolar echinococcosis (AE) respectively, are the two main species of interest from a human and veterinary perspective. This review collates the current state-of-the-art understanding of these two parasites within four key areas of relevance to human and veterinary professionals: transmission and epidemiology, clinical signs and pathogenesis, diagnosis, and treatment and prevention. This review should serve as a broad introduction to the most important Echinococcus spp. The reader is advised to seek out specific literature on individual diseases and their causative parasites for a deeper understanding.
Topics: Animals; Echinococcosis; Echinococcus granulosus; Echinococcus multilocularis; Humans
PubMed: 33246571
DOI: 10.1016/j.rvsc.2020.11.010 -
PLoS Pathogens Dec 2021Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to... (Review)
Review
Schistosomes are long lived, intravascular parasitic platyhelminths that infect >200 million people globally. The molecular mechanisms used by these blood flukes to dampen host immune responses are described in this review. Adult worms express a collection of host-interactive tegumental ectoenzymes that can cleave host signaling molecules such as the "alarmin" ATP (cleaved by SmATPDase1), the platelet activator ADP (SmATPDase1, SmNPP5), and can convert AMP into the anti-inflammatory mediator adenosine (SmAP). SmAP can additionally cleave the lipid immunomodulator sphingosine-1-phosphate and the proinflammatory anionic polymer, polyP. In addition, the worms release a barrage of proteins (e.g., SmCB1, SjHSP70, cyclophilin A) that can impinge on immune cell function. Parasite eggs also release their own immunoregulatory proteins (e.g., IPSE/α1, omega1, SmCKBP) as do invasive cercariae (e.g., Sm16, Sj16). Some schistosome glycans (e.g., LNFPIII, LNnT) and lipids (e.g., Lyso-PS, LPC), produced by several life stages, likewise affect immune cell responses. The parasites not only produce eicosanoids (e.g., PGE2, PGD2-that can be anti-inflammatory) but can also induce host cells to release these metabolites. Finally, the worms release extracellular vesicles (EVs) containing microRNAs, and these too have been shown to skew host cell metabolism. Thus, schistosomes employ an array of biomolecules-protein, lipid, glycan, nucleic acid, and more, to bend host biochemistry to their liking. Many of the listed molecules have been individually shown capable of inducing aspects of the polarized Th2 response seen following infection (with the generation of regulatory T cells (Tregs), regulatory B cells (Bregs) and anti-inflammatory, alternatively activated (M2) macrophages). Precisely how host cells integrate the impact of these myriad parasite products following natural infection is not known. Several of the schistosome immunomodulators described here are in development as novel therapeutics against autoimmune, inflammatory, and other, nonparasitic, diseases.
Topics: Animals; Helminth Proteins; Humans; Immunologic Factors; Schistosoma; Schistosomiasis
PubMed: 34969052
DOI: 10.1371/journal.ppat.1010064 -
Trends in Parasitology Dec 2022Intravascular schistosomes may control immune and hemostatic responses by regulating the nature and amount of selected host purinergic signaling molecules - such as... (Review)
Review
Intravascular schistosomes may control immune and hemostatic responses by regulating the nature and amount of selected host purinergic signaling molecules - such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and nicotinamide adenine dinucleotide (NAD) - surrounding them. Such metabolites are collectively known as the worm's 'purinergic halo'. Host-interactive, membrane-bound, tegumental ectonucleotidases, notably SmATPDase1, SmNPP5, SmAP and SmNACE, can degrade proinflammatory, prothrombotic and immunomodulatory purinergic metabolites like those listed. A common catabolic product is the anti-inflammatory metabolite adenosine that can additionally be taken in by the worms as food. We envision the tegumental ectonucleotidases as having a twofold role at the worm surface: first, they degrade potentially harmful host signaling molecules, and second, they generate vital nutrients around the worms from where these can be conveniently imported.
Topics: Animals; Schistosoma mansoni
PubMed: 36182536
DOI: 10.1016/j.pt.2022.09.001 -
Marine Drugs Jan 2021Marine invertebrates are promising sources of novel bioactive secondary metabolites, and organisms like sponges, ascidians and nudibranchs are characterised by... (Review)
Review
Marine invertebrates are promising sources of novel bioactive secondary metabolites, and organisms like sponges, ascidians and nudibranchs are characterised by possessing potent defensive chemicals. Animals that possess chemical defences often advertise this fact with aposematic colouration that potential predators learn to avoid. One seemingly defenceless group that can present bright colouration patterns are flatworms of the order Polycladida. Although members of this group have typically been overlooked due to their solitary and benthic nature, recent studies have isolated the neurotoxin tetrodotoxin from these mesopredators. This review considers the potential of polyclads as potential sources of natural products and reviews what is known of the activity of the molecules found in these animals. Considering the ecology and diversity of polyclads, only a small number of species from both suborders of Polycladida, Acotylea and Cotylea have been investigated for natural products. As such, confirming assumptions as to which species are in any sense toxic or if the compounds they use are biosynthesised, accumulated from food or the product of symbiotic bacteria is difficult. However, further research into the group is suggested as these animals often display aposematic colouration and are known to prey on invertebrates rich in bioactive secondary metabolites.
Topics: Animals; Biological Products; Platyhelminths; Protein Structure, Secondary; Protein Structure, Tertiary; Secondary Metabolism
PubMed: 33494164
DOI: 10.3390/md19020047 -
PLoS Neglected Tropical Diseases Apr 2020Schistosomes are parasitic blood flukes that infect >200 million people around the world. Free-swimming larval stages penetrate the skin, invade a blood vessel, and... (Review)
Review
Schistosomes are parasitic blood flukes that infect >200 million people around the world. Free-swimming larval stages penetrate the skin, invade a blood vessel, and migrate through the heart and lungs to the vasculature of the liver, where maturation and mating occurs. From here, the parasite couples migrate to their preferred egg laying sites. Here, we compare and contrast what is known about the migration patterns within the definitive host of the three major species of human schistosome: Schistosoma mansoni, S. japonicum, and S. haematobium. We conclude that intravascular schistosomes are inexorable colonizers whose migration and egg laying strategy is profligate; all three species (and their eggs) can be found throughout the mesenteric venules, the rectal venous plexus, and, to a greater or lesser extent, the urogenital venous plexuses. In addition, it is common for parasite eggs to be deposited in locations that lack easy access to the exterior, further demonstrating the relentless exploratory nature of these intravascular worms.
Topics: Animals; Blood Vessels; Humans; Life Cycle Stages; Locomotion; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis haematobia; Schistosomiasis japonica; Schistosomiasis mansoni
PubMed: 32240157
DOI: 10.1371/journal.pntd.0007951 -
Cell Proliferation Sep 2022Planarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong... (Review)
Review
BACKGROUND
Planarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong regeneration ability. Both the complexity of multiple regulatory networks and their coordinate functions contribute to the maintenance of normal cellular homeostasis and the process of regeneration in planarian. The polarity, size, location and number of regeneration tissues are regulated by diverse mechanisms. In this review we summarize the recent advances about the importance genetic and molecular mechanisms for regeneration control on various tissues in planarian.
METHODS
A comprehensive literature search of original articles published in recent years was performed in regards to the molecular mechanism of each cell types during the planarian regeneration, including neoblast, nerve system, eye spot, excretory system and epidermal.
RESULTS
Available molecular mechanisms gave us an overview of regeneration process in every tissue. The sense of injuries and initiation of regeneration is regulated by diverse genes like follistatin and ERK signaling. The Neoblasts differentiate into tissue progenitors under the regulation of genes such as egfr-3. The regeneration polarity is controlled by Wnt pathway, BMP pathway and bioelectric signals. The neoblast within the blastema differentiate into desired cell types and regenerate the missing tissues. Those tissue specific genes regulate the tissue progenitor cells to differentiate into desired cell types to complete the regeneration process.
CONCLUSION
All tissue types in planarian participate in the regeneration process regulated by distinct molecular factors and cellular signaling pathways. The neoblasts play vital roles in tissue regeneration and morphology maintenance. These studies provide new insights into the molecular mechanisms for regulating planarian regeneration.
Topics: Animals; Homeostasis; Models, Biological; Planarians; Signal Transduction; Stem Cells
PubMed: 35811385
DOI: 10.1111/cpr.13276 -
Parasitology Sep 2022In the present paper, we review two of the most neglected intestinal food-borne trematodiases: echinostomiasis, caused by members of the family Echinostomatidae, and... (Review)
Review
In the present paper, we review two of the most neglected intestinal food-borne trematodiases: echinostomiasis, caused by members of the family Echinostomatidae, and gastrodiscoidiasis produced by the amphistome . Both parasitic infections are important intestinal food-borne diseases. Humans become infected after ingestion of raw or insufficiently cooked molluscs, fish, crustaceans, amphibians or aquatic vegetables. Thus, eating habits are essential to determine the distribution of these parasitic diseases and, traditionally, they have been considered as minor diseases confined to low-income areas, mainly in Asia. However, this scenario is changing and the population at risk are currently expanding in relation to factors such as new eating habits in developed countries, growing international markets, improved transportation systems and demographic changes. These aspects determine the necessity of a better understanding of these parasitic diseases. Herein, we review the main features of human echinostomiasis and gastrodiscoidiasis in relation to their biology, epidemiology, immunology, clinical aspects, diagnosis and treatment.
Topics: Animals; Echinostomatidae; Echinostomiasis; Humans; Parasitic Diseases; Trematoda; Trematode Infections
PubMed: 35343418
DOI: 10.1017/S0031182022000385 -
Nucleic Acids Research Mar 2022Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the...
Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the primary cause of morbidity. In addition, helminth infections of cattle have a significant economic impact on livestock production, milk yield and fertility. The etiological agents of helminth infections are mainly Nematodes (roundworms) and Platyhelminths (flatworms). G-quadruplexes (G4) are unusual nucleic acid structures formed by G-rich sequences that can be recognized by specific G4 ligands. Here we used the G4Hunter Web Tool to identify and compare potential G4 sequences (PQS) in the nuclear and mitochondrial genomes of various helminths to identify G4 ligand targets. PQS are nonrandomly distributed in these genomes and often located in the proximity of genes. Unexpectedly, a Nematode, Ascaris lumbricoides, was found to be highly enriched in stable PQS. This species can tolerate high-stability G4 structures, which are not counter selected at all, in stark contrast to most other species. We experimentally confirmed G4 formation for sequences found in four different parasitic helminths. Small molecules able to selectively recognize G4 were found to bind to Schistosoma mansoni G4 motifs. Two of these ligands demonstrated potent activity both against larval and adult stages of this parasite.
Topics: Animals; Cattle; G-Quadruplexes; Genome; Helminths; Humans; Ligands; Nematoda; Parasites; Platyhelminths
PubMed: 35234933
DOI: 10.1093/nar/gkac129 -
Parasitology Sep 2022Foodborne trematodes (FBT) of public health significance include liver flukes ( and ), lung flukes ( and several other spp.) and intestinal flukes, which include... (Review)
Review
Foodborne trematodes (FBT) of public health significance include liver flukes ( and ), lung flukes ( and several other spp.) and intestinal flukes, which include heterophyids ( and ), echinostomes ( and ) and miscellaneous species, including and . These trematode infections are distributed worldwide but occur most commonly in Asia. The global burden of FBT diseases has been estimated at about 80 million, however, this seems to be a considerable underestimate. Their life cycle involves a molluscan first intermediate host, and a second intermediate host, including freshwater fish, crustaceans, aquatic vegetables and freshwater or brackish water gastropods and bivalves. The mode of human infection is the consumption of the second intermediate host under raw or improperly cooked conditions. The major pathogenesis of and spp. infection includes inflammation of the bile duct which leads to cholangitis and cholecystitis, and in a substantial number of patients, serious complications, such as liver cirrhosis and cholangiocarcinoma, may develop. In lung fluke infections, cough, bloody sputum and bronchiectasis are the most common clinical manifestations. However, lung flukes often migrate to extrapulmonary sites, including the brain, spinal cord, skin, subcutaneous tissues and abdominal organs. Intestinal flukes can induce inflammation in the intestinal mucosa, and they may at times undergo extraintestinal migration, in particular, in immunocompromised patients. In order to control FBT infections, eating foods after proper cooking is strongly recommended.
Topics: Animals; Echinostoma; Fascioliasis; Heterophyidae; Humans; Inflammation; Trematoda; Trematode Infections
PubMed: 35591777
DOI: 10.1017/S0031182022000725