Uptake of Schistosoma mansoni extracellular vesicles by human endothelial and monocytic cell lines and impact on vascular endothelial cell gene expression

Kifle, Desalegn Woldeyohannes; Chaiyadet, Sujittra; Waardenberg, Ashley J.; Wise, Ingrid; Cooper, Martha M; Becker, Luke; Doolan, Denise L.; Laha, Thewarach; Sotillo, Javier; Pearson, Mark S.; Loukas, Alex

doi:10.1016/j.ijpara.2020.05.005

Cited by 38 publications

(29 citation statements)

References 86 publications

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“…Curiously, the anti-schistosomal activities of compound 12, a lipophilic derivative of Sclareol, a plant-derived diterpenoid widely used as a fragrance and flavoring substance, were reported to be specifically associated with higher abundance of ARA within the metabolite pool of treated worms when compared to controls ( 43 ), additionally implicating ARA as a parasite endogenous schistosomicide. On another aspect, exosome-like vesicles derived from adult S. mansoni were found to be internalized by vascular endothelial cells and monocytes and to powerfully up regulate ARA metabolism ( 44 ), a remarkable host defense mechanism as ARA and other unsaturated fatty acids and some of their metabolites function as endogenous antimicrobial molecules ( 45 ).…”

Section: Arachidonic Acid Is An Endoschistosomicide In the Final Mammmentioning

confidence: 99%

Arachidonic Acid Is a Safe and Efficacious Schistosomicide, and an Endoschistosomicide in Natural and Experimental Infections, and Cysteine Peptidase Vaccinated Hosts

2020

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Blood flukes of the genus Schistosoma are covered by a protective heptalaminated, double lipid bilayer surface membrane. Large amounts of sphingomyelin (SM) in the outer leaflet form with surrounding water molecules a tight hydrogen bond barrier, which allows entry of nutrients and prevents access of host immune effectors. Excessive hydrolysis of SM to phosphoryl choline and ceramide via activation of the parasite tegument-associated neutral sphingomyelinase (nSMase) with the polyunsaturated fatty acid, arachidonic acid (ARA) leads to parasite death, via allowing exposure of apical membrane antigens to antibody-dependent cell-mediated cytotoxicity (ADCC), and accumulation of the pro-apoptotic ceramide. Surface membrane nSMase represents, thus, a worm Achilles heel, and ARA a valid schistosomicide. Several experiments conducted in vitro using larval, juvenile, and adult Schistosoma mansoni and Schistosoma haematobium documented ARA schistosomicidal potential. Arachidonic acid schistosomicidal action was shown to be safe and efficacious in mice and hamsters infected with S. mansoni and S. haematobium , respectively, and in children with light S. mansoni infection. A combination of praziquantel and ARA led to outstanding cure rates in children with heavy S. mansoni infection. Additionally, ample evidence was obtained for the powerful ARA ovocidal potential in vivo and in vitro against S. mansoni and S. haematobium liver and intestine eggs. Studies documented ARA as an endogenous schistosomicide in the final mammalian and intermediate snail hosts, and in mice and hamsters, immunized with the cysteine peptidase-based vaccine. These findings together support our advocating the nutrient ARA as the safe and efficacious schistosomicide of the future.

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Section: Arachidonic Acid Is An Endoschistosomicide In the Final Mammmentioning

confidence: 99%

Arachidonic Acid Is a Safe and Efficacious Schistosomicide, and an Endoschistosomicide in Natural and Experimental Infections, and Cysteine Peptidase Vaccinated Hosts

2020

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“…In trematodes, TSPs are involved in tegument development [ 84 , 85 , 86 ]. TSP LELs have been tested as vaccine candidates in trematode models of infection [ 42 , 47 , 87 ] and antibodies produced against TSP vaccine candidates present in S. mansoni and O. viverrini EVs blocked the internalization of EVs through host cells in both parasites, and decreased pathogenesis in the case of O. viverrini [ 29 , 42 , 88 ], suggesting a possible mechanism of vaccine efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…It could be that vaccination with the EV molecules described herein is eliciting similar immune mechanisms to engender the observed anti-fecundity effects, which may be manifesting in a reduction of the fitness and fecundity of adult worms and/or a shortening of the lifespan of eggs embolized in the tissues [ 91 ]. Furthermore, we have reported on the capacity of helminth EVs to promote pathogenesis via their endocytosis by host cells and subsequent manipulation of host immune effector mechanisms, such as an increase in IL-6 secretion [ 29 ] and differential expression of genes involved in immune cell trafficking [ 88 ], and the ability of antibodies against helminth EV proteins, such as TSPs, to block vesicle uptake [ 29 , 42 , 88 ] provides a plausible mechanism for protective efficacy.…”

Section: Discussionmentioning

confidence: 99%

Schistosoma haematobium Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis

et al. 2020

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Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120 k pellet vesicles and microvesicle-like, 15 k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120 k pellet vesicles and larger 15 k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-transferase, saponins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.

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“…The study of Mekonnen et al (2020) reported that ShTSP-2 conferred a highly significant protection against heterologous challenge (S. mansoni) model of infection. However, it is not clear how the ability of anti-TSP antibodies to block vesicle uptake by host target cells explains the potential of TSPs as promising anti-fluke vaccine (Kifle et al 2020b).…”

Section: Schistosoma Mansoni 14 Kda Fatty Acid Binding Proteinmentioning

confidence: 99%

“…The Sm-p80 immunogen may interact with vaccine-induced specific antibodies, leading to activation of effector cells and release of inflammatory mediators. Calpain was recently found to be enriched in EV (Kifle et al 2020a), and when it interacts with antibodies, calpain/ antibody complexes can be internalized by the host and may enhance the production of arachidonic acid, and immune cells activation and trafficking (Kifle et al 2020b).…”

Section: Sm-p80mentioning

confidence: 99%

A comprehensive and critical overview of schistosomiasis vaccine candidates

et al. 2021

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Uptake of Schistosoma mansoni extracellular vesicles by human endothelial and monocytic cell lines and impact on vascular endothelial cell gene expression

Cited by 38 publications

References 86 publications

Arachidonic Acid Is a Safe and Efficacious Schistosomicide, and an Endoschistosomicide in Natural and Experimental Infections, and Cysteine Peptidase Vaccinated Hosts

Arachidonic Acid Is a Safe and Efficacious Schistosomicide, and an Endoschistosomicide in Natural and Experimental Infections, and Cysteine Peptidase Vaccinated Hosts

Schistosoma haematobium Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis

A comprehensive and critical overview of schistosomiasis vaccine candidates

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