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2. Combinatorial multimer staining and spectral flow cytometry facilitate quantification and characterization of polysaccharide-specific B cell immunity

Author

Hoving, Dennis, Marques, Alexandre H. C., Huisman, Wesley, Nosoh, Beckley A., de Kroon, Alicia C., van Hengel, Oscar R. J., Wu, Bing-Ru, Steenbergen, Rosanne A. M., van Helden, Pauline M., Urban, Britta C., Dhar, Nisha, Ferreira, Daniela M., Kwatra, Gaurav, Hokke, Cornelis H., and Jochems, Simon P.

Published
2023
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4. Safety and infectivity of female cercariae in Schistosoma-naïve, healthy participants: a controlled human Schistosoma mansoni infection study

Author

Koopman, Jan Pieter R., Houlder, Emma L., Janse, Jacqueline J., Casacuberta-Partal, Miriam, Lamers, Olivia A.C., Sijtsma, Jeroen C., de Dood, Claudia, Hilt, Stan T., Ozir-Fazalalikhan, Arifa, Kuiper, Vincent P., Roozen, Geert V.T., de Bes-Roeleveld, Laura M., Kruize, Yvonne C.M., Wammes, Linda J., Smits, Hermelijn H., van Lieshout, Lisette, van Dam, Govert J., van Amerongen-Westra, Inge M., Meij, Pauline, Corstjens, Paul L.A.M., Jochems, Simon P., van Diepen, Angela, Yazdanbakhsh, Maria, Hokke, Cornelis H., and Roestenberg, Meta

Published
2023
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6. S. mansoni -derived omega-1 prevents OVA-specific allergic airway inflammation via hampering of cDC2 migration.

Author

Patente, Thiago A., Gasan, Thomas A., Scheenstra, Maaike, Ozir-Fazalalikhan, Arifa, Obieglo, Katja, Schetters, Sjoerd, Verwaerde, Stijn, Vergote, Karl, Otto, Frank, Wilbers, Ruud H. P., van Bloois, Eline, Wijck, Yolanda van, Taube, Christian, Hammad, Hamida, Schots, Arjen, Everts, Bart, Yazdanbakhsh, Maria, Guigas, Bruno, Hokke, Cornelis H., and Smits, Hermelijn H.

Subjects
REGULATORY T cells, MYELOID cells, SCHISTOSOMA mansoni, PERITONEUM, DENDRITIC cells
Abstract

Chronic infection with Schistosoma mansoni parasites is associated with reduced allergic sensitization in humans, while schistosome eggs protects against allergic airway inflammation (AAI) in mice. One of the main secretory/excretory molecules from schistosome eggs is the glycosylated T2-RNAse Omega-1 (ω1). We hypothesized that ω1 induces protection against AAI during infection. Peritoneal administration of ω1 prior to sensitization with Ovalbumin (OVA) reduced airway eosinophilia and pathology, and OVA-specific Th2 responses upon challenge, independent from changes in regulatory T cells. ω1 was taken up by monocyte-derived dendritic cells, mannose receptor (CD206)-positive conventional type 2 dendritic cells (CD206+ cDC2), and by recruited peritoneal macrophages. Additionally, ω1 impaired CCR7, F-actin, and costimulatory molecule expression on myeloid cells and cDC2 migration in and ex vivo, as evidenced by reduced OVA+ CD206+ cDC2 in the draining mediastinal lymph nodes (medLn) and retainment in the peritoneal cavity, while antigen processing and presentation in cDC2 were not affected by ω1 treatment. Importantly, RNAse mutant ω1 was unable to reduce AAI or affect DC migration, indicating that ω1 effects are dependent on its RNAse activity. Altogether, ω1 hampers migration of OVA+ cDC2 to the draining medLn in mice, elucidating how ω1 prevents allergic airway inflammation in the OVA/alum mouse model. Author summary: Asthma is a chronic inflammatory disease, leading to cough, wheeze, and shortness of breath. The prevalence has increased drastically in Westernized societies and is now increasing in low- and middle-income countries. Chronic infection with the parasitic helminth, Schistosoma (S.) mansoni protects against allergic airway inflammation (AAI) in mice, and is associated with reduced skin prick test positivity to inhaled allergens in humans. Here we show that peritoneal administration of ω1, a single glycoprotein secreted by S. mansoni eggs, reduced OVA/alum-induced AAI. ω1 is taken up in the peritoneal cavity by dendritic cells (DCs) expressing the mannose receptor, reducing their expression of CCR7 and migratory capacity to the draining mediastinal lymph nodes. This results in accumulation of DCs in the peritoneal cavity of allergic mice and reduced numbers of DCs reaching the draining lymph nodes. The effects observed for ω1 is dependent on its RNAse activity, since the RNAse mutant form of ω1 was unable to reduce AAI nor affect DC migration. Our findings provide insights into how ω1 can modulated the immune response during allergic inflammation, and this may open new avenues for the development of novel therapeutic strategies for allergic asthma. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells

Author

Chayé, Mathilde A. M., primary, Gasan, Thomas A., additional, Ozir-Fazalalikhan, Arifa, additional, Scheenstra, Maaike R., additional, Zawistowska-Deniziak, Anna, additional, van Hengel, Oscar R. J., additional, Gentenaar, Max, additional, Manurung, Mikhael D., additional, Harvey, Michael R., additional, Codée, Jeroen D. C., additional, Chiodo, Fabrizio, additional, Heijke, Anouk M., additional, Kalinowska, Alicja, additional, van Diepen, Angela, additional, Hensbergen, Paul J., additional, Yazdanbakhsh, Maria, additional, Guigas, Bruno, additional, Hokke, Cornelis H., additional, and Smits, Hermelijn H., additional

Published
2023
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10. Life stage-specific glycosylation of extracellular vesicles from Schistosoma mansoni schistosomula and adult worms drives differential interaction with C-type lectin receptors DC-SIGN and MGL

Author

Kuipers, Marije E., primary, Nguyen, D. Linh, additional, van Diepen, Angela, additional, Mes, Lynn, additional, Bos, Erik, additional, Koning, Roman I., additional, Nolte-’t Hoen, Esther N. M., additional, Smits, Hermelijn H., additional, and Hokke, Cornelis H., additional

Published
2023
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11. Identification of CAA as highly specific and sensitive antibody target for acute schistosomiasis diagnostics

Author

Kildemoes, Anna O., primary, Veldhuizen, Tom, additional, Hilt, Stan T., additional, van Lieshout, Lisette, additional, Supali, Taniawati, additional, Sartono, Erliyani, additional, Yazdanbakhsh, Maria, additional, Camprubí-Ferrer, Daniel, additional, Muñoz, Jose, additional, Clerinx, Joannes, additional, Corstjens, Paul L.A.M., additional, van Dam, Govert J., additional, Visser, Leo G., additional, Roestenberg, Meta, additional, van Diepen, Angela, additional, and Hokke, Cornelis H., additional

Published
2023
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12. Unraveling cross-reactivity of anti-glycan IgG responses in filarial nematode infections

Author

Petralia, Laudine M. C., primary, van Diepen, Angela, additional, Nguyen, Dieu-Linh, additional, Lokker, Lena A., additional, Sartono, Erliyani, additional, Bennuru, Sasisekhar, additional, Nutman, Thomas B., additional, Pfarr, Kenneth, additional, Hoerauf, Achim, additional, Wanji, Samuel, additional, Foster, Jeremy M., additional, and Hokke, Cornelis H., additional

Published
2023
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13. Ostertagia ostertagi activation-associated secreted protein 1 (OSP-2) mRNA, complete cds.

Author

Zwanenburg, Laurens, Borloo, Jimmy, Decorte, Bregt, Bunte, Myrna, Mokhtari, Sanaz, Serna, Sonia, Reichardt, Niels C., Seys, Leen J.M., van Diepen, Angela, Schots, Arjen, Wilbers, Ruud, Hokke, Cornelis H., Claerebout, Edwin, Geldhof, Peter, Zwanenburg, Laurens, Borloo, Jimmy, Decorte, Bregt, Bunte, Myrna, Mokhtari, Sanaz, Serna, Sonia, Reichardt, Niels C., Seys, Leen J.M., van Diepen, Angela, Schots, Arjen, Wilbers, Ruud, Hokke, Cornelis H., Claerebout, Edwin, and Geldhof, Peter

Published
2023

14. Special considerations for studies of extracellular vesicles from parasitic helminths: A community‐led roadmap to increase rigour and reproducibility

Author

White, Ruby, Sotillo, Javier, Ancarola, María Eugenia, Borup, Anne, Boysen, Anders Toftegaard, Brindley, Paul J, Buzás, Edit I, Cavallero, Serena, Chaiyadet, Sujittra, Chalmers, Iain W, Cucher, Marcela A, Dagenais, Maude, Davis, Chelsea N, Devaney, Eileen, Duque-Correa, Maria A, Eichenberger, Ramon M; https://orcid.org/0000-0002-9337-9616, Fontenla, Santiago, Gasan, Thomas A, Hokke, Cornelis H, Kosanovic, Maja, Kuipers, Marije E, Laha, Thewarach, Loukas, Alex, Maizels, Rick M, Marcilla, Antonio, Mazanec, Hynek, Morphew, Russell M, Neophytou, Kyriaki, Nguyen, Linh Thuy, Nolte‐‘t Hoen, Esther, et al, White, Ruby, Sotillo, Javier, Ancarola, María Eugenia, Borup, Anne, Boysen, Anders Toftegaard, Brindley, Paul J, Buzás, Edit I, Cavallero, Serena, Chaiyadet, Sujittra, Chalmers, Iain W, Cucher, Marcela A, Dagenais, Maude, Davis, Chelsea N, Devaney, Eileen, Duque-Correa, Maria A, Eichenberger, Ramon M; https://orcid.org/0000-0002-9337-9616, Fontenla, Santiago, Gasan, Thomas A, Hokke, Cornelis H, Kosanovic, Maja, Kuipers, Marije E, Laha, Thewarach, Loukas, Alex, Maizels, Rick M, Marcilla, Antonio, Mazanec, Hynek, Morphew, Russell M, Neophytou, Kyriaki, Nguyen, Linh Thuy, Nolte‐‘t Hoen, Esther, and et al

Abstract

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved.

Published
2023

15. Special considerations for studies of extracellular vesicles from parasitic helminths: A community‐led roadmap to increase rigour and reproducibility

Author

White, Ruby, primary, Sotillo, Javier, additional, Ancarola, María Eugenia, additional, Borup, Anne, additional, Boysen, Anders Toftegaard, additional, Brindley, Paul J., additional, Buzás, Edit I., additional, Cavallero, Serena, additional, Chaiyadet, Sujittra, additional, Chalmers, Iain W., additional, Cucher, Marcela A., additional, Dagenais, Maude, additional, Davis, Chelsea N., additional, Devaney, Eileen, additional, Duque‐Correa, Maria A., additional, Eichenberger, Ramon Marc, additional, Fontenla, Santiago, additional, Gasan, Thomas A., additional, Hokke, Cornelis H., additional, Kosanovic, Maja, additional, Kuipers, Marije E., additional, Laha, Thewarach, additional, Loukas, Alex, additional, Maizels, Rick M., additional, Marcilla, Antonio, additional, Mazanec, Hynek, additional, Morphew, Russell M., additional, Neophytou, Kyriaki, additional, Nguyen, Linh Thuy, additional, Nolte‐‘t Hoen, Esther, additional, Povelones, Michael, additional, Robinson, Mark W., additional, Rojas, Alicia, additional, Schabussova, Irma, additional, Smits, Hermelijn H., additional, Sungpradit, Sivapong, additional, Tritten, Lucienne, additional, Whitehead, Bradley, additional, Zakeri, Amin, additional, Nejsum, Peter, additional, Buck, Amy H., additional, and Hoffmann, Karl F., additional

Published
2023
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16. Alteration of rhesus macaque serum N-glycome during infection with the human parasitic filarial nematode Brugia malayi

Author

Petralia, Laudine M.C., primary, Santha, Esrath, additional, Behrens, Anna-Janina, additional, Nguyen, D. Linh, additional, Ganatra, Mehul B., additional, Taron, Christopher H., additional, Khatri, Vishal, additional, Kalyanasundaram, Ramaswamy, additional, Diepen, Angela van, additional, Hokke, Cornelis H., additional, and Foster, Jeremy M., additional

Published
2022
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17. Mass Spectrometric and Glycan Microarray–Based Characterization of the Filarial Nematode Brugia malayi Glycome Reveals Anionic and Zwitterionic Glycan Antigens

Author

Petralia, Laudine M.C., primary, van Diepen, Angela, additional, Lokker, Lena A., additional, Nguyen, D. Linh, additional, Sartono, Erliyani, additional, Khatri, Vishal, additional, Kalyanasundaram, Ramaswamy, additional, Taron, Christopher H., additional, Foster, Jeremy M., additional, and Hokke, Cornelis H., additional

Published
2022
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18. Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

Author

Medical Research Council (UK), Rosetrees Trust, Fondation Dormeur, Vaduz, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), NHS Foundation Trust, Kings College London, Ministerio de Educación y Ciencia (España), Agencia Estatal de Investigación (España), Wellcome Trust, Ministerio de Ciencia, Innovación y Universidades (España), Biotechnology and Biological Sciences Research Council (UK), Bill & Melinda Gates Foundation, Ministry of Foreign Affairs (Denmark), Irish Aid, World Bank Group, Ministry of Foreign Affairs (The Netherlands), Norwegian Agency for Development Cooperation, European Commission, Department for International Development (UK), United States Agency for International Development, Huettner, Isabella, Krumm, Stefanie A., Serna, Sonia, Brzezicka, Katarzyna, Monaco, Serena, Walpole, Samuel, van Diepen, Angela, Allan, Fiona, Hicks,Thomas, Kimuda, Simon, Emery, Aidan M., Landais, Elise, Hokke, Cornelis H., Angulo, Jesús, Reichardt, Niels, Doores, Katie J, Medical Research Council (UK), Rosetrees Trust, Fondation Dormeur, Vaduz, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), NHS Foundation Trust, Kings College London, Ministerio de Educación y Ciencia (España), Agencia Estatal de Investigación (España), Wellcome Trust, Ministerio de Ciencia, Innovación y Universidades (España), Biotechnology and Biological Sciences Research Council (UK), Bill & Melinda Gates Foundation, Ministry of Foreign Affairs (Denmark), Irish Aid, World Bank Group, Ministry of Foreign Affairs (The Netherlands), Norwegian Agency for Development Cooperation, European Commission, Department for International Development (UK), United States Agency for International Development, Huettner, Isabella, Krumm, Stefanie A., Serna, Sonia, Brzezicka, Katarzyna, Monaco, Serena, Walpole, Samuel, van Diepen, Angela, Allan, Fiona, Hicks,Thomas, Kimuda, Simon, Emery, Aidan M., Landais, Elise, Hokke, Cornelis H., Angulo, Jesús, Reichardt, Niels, and Doores, Katie J

Abstract

The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.

Published
2022

20. Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19

Author

Pongracz, Tamas, primary, Nouta, Jan, additional, Wang, Wenjun, additional, van Meijgaarden, Krista E., additional, Linty, Federica, additional, Vidarsson, Gestur, additional, Joosten, Simone A., additional, Ottenhoff, Tom H.M., additional, Hokke, Cornelis H., additional, de Vries, Jutte J.C., additional, Arbous, Sesmu M., additional, Roukens, Anna H.E., additional, and Wuhrer, Manfred, additional

Published
2022
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21. Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

Author

Huettner, Isabella, primary, Krumm, Stefanie A., additional, Serna, Sonia, additional, Brzezicka, Katarzyna, additional, Monaco, Serena, additional, Walpole, Samuel, additional, van Diepen, Angela, additional, Allan, Fiona, additional, Hicks, Thomas, additional, Kimuda, Simon, additional, Emery, Aidan M., additional, Landais, Elise, additional, Hokke, Cornelis H., additional, Angulo, Jesus, additional, Reichardt, Niels, additional, Doores, Katie J., additional, Allen, Susan, additional, Kilembe, William, additional, Lakhi, Shabir, additional, Inambao, Mubiana, additional, Karita, Etienne, additional, Kamali, Anatoli, additional, Sanders, Eduard J., additional, Anzala, Omu, additional, Edward, Vinodh, additional, Bekker, Linda-Gail, additional, Tang, Jianming, additional, Gilmour, Jill, additional, Hunter, Eric, additional, and Price, Matt, additional

Published
2022
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22. Schistosoma mansoni α-N-acetylgalactosaminidase (SmNAGAL) regulates coordinated parasite movement and egg production

Author

Hulme, Benjamin J., primary, Geyer, Kathrin K., additional, Forde-Thomas, Josephine E., additional, Padalino, Gilda, additional, Phillips, Dylan W., additional, Ittiprasert, Wannaporn, additional, Karinshak, Shannon E., additional, Mann, Victoria H., additional, Chalmers, Iain W., additional, Brindley, Paul J., additional, Hokke, Cornelis H., additional, and Hoffmann, Karl F., additional

Published
2022
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23. Excretion patterns of Schistosoma mansoni antigens CCA and CAA by adult male and female worms, using a mouse model and ex vivo parasite cultures

Author

Casacuberta-Partal, Miriam, primary, van Lieshout, Lisette, additional, van Diepen, Angela, additional, Sijtsma, Jeroen, additional, Ozir-Fazalalikhan, Arifa, additional, Koopman, Jan Pieter R., additional, de Dood, Claudia J., additional, Corstjens, Paul L.A.M., additional, van Dam, Govert J., additional, Hokke, Cornelis H., additional, and Roestenberg, Meta, additional

Published
2021
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24. Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study

Author

Pearson, Mark S, primary, Tedla, Bemnet A, additional, Mekonnen, Gebeyaw G, additional, Proietti, Carla, additional, Becker, Luke, additional, Nakajima, Rie, additional, Jasinskas, Al, additional, Doolan, Denise L, additional, Amoah, Abena S, additional, Knopp, Stefanie, additional, Rollinson, David, additional, Ali, Said M, additional, Kabole, Fatma, additional, Hokke, Cornelis H, additional, Adegnika, Akim A, additional, Field, Matt A, additional, van Dam, Govert, additional, Corstjens, Paul L A M, additional, Mduluza, Takafira, additional, Mutapi, Francisca, additional, Oeuvray, Claude, additional, Greco, Beatrice, additional, Chaiyadet, Sujittra, additional, Laha, Thewarach, additional, Cai, Pengfei, additional, McManus, Donald P, additional, Bottazzi, Maria Elena, additional, Felgner, Philip L, additional, Sotillo, Javier, additional, and Loukas, Alex, additional

Published
2021
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25. Screening of a Library of Recombinant Schistosoma mansoni Proteins With Sera From Murine and Human Controlled Infections Identifies Early Serological Markers.

Author

Crosnier, Cécile, Hokke, Cornelis H, Protasio, Anna V, Brandt, Cordelia, Rinaldi, Gabriel, Langenberg, Marijke C C, Clare, Simon, Janse, Jacqueline J, Wilson, Shona, Berriman, Matthew, Roestenberg, Meta, and Wright, Gavin J

Subjects
*SCHISTOSOMIASIS diagnosis, *TREMATODA, *ISOQUINOLINE, *SCHISTOSOMIASIS, *RESEARCH funding, *MAMMALS, *PARASITES, *RECOMBINANT proteins
Abstract

Background: Schistosomiasis is a major global health problem caused by blood-dwelling parasitic worms, which is currently tackled primarily by mass administration of the drug praziquantel. Appropriate drug treatment strategies are informed by diagnostics that establish the prevalence and intensity of infection, which, in regions of low transmission, should be highly sensitive.Methods: To identify sensitive new serological markers of Schistosoma mansoni infections, we have compiled a recombinant protein library of parasite cell-surface and secreted proteins expressed in mammalian cells.Results: Together with a time series of sera samples from volunteers experimentally infected with a defined number of male parasites, we probed this protein library to identify several markers that can detect primary infections with as low as 10 parasites and as early as 5 weeks postinfection.Conclusions: These new markers could be further explored as valuable tools to detect ongoing and previous S mansoni infections, including in endemic regions where transmission is low. [ABSTRACT FROM AUTHOR]

Published
2022
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26. Optimized Protocol for the Isolation of Extracellular Vesicles from the Parasitic Worm with Improved Purity, Concentration, and Yield.

Author

Kuipers, Marije E., Koning, Roman I., Bos, Erik, Hokke, Cornelis H., Smits, Hermelijn H., and Nolte-'t Hoen, Esther N. M.

Subjects
SCHISTOSOMA mansoni, HELMINTHS, EXTRACELLULAR vesicles, BLOOD products, SUCROSE
Abstract

In the past decade, the interest in helminth-derived extracellular vesicles (EVs) increased owing to their role in pathogen-host communication. However, the availability of EVs from these parasitic worms is often limited due to the restricted occurrence and culturing possibilities of these organisms. Schistosoma mansoni is one of several helminths that have been shown to release EVs affecting the immune response of their host. Further investigation of mechanisms underlying these EV-induced effects warrants separation of EVs from other components of the helminth excretory/secretory products. However, isolation of high-purity EVs often come to the expense of reduced EV yield. We therefore aimed to develop an optimized protocol for isolation of EVs from S. mansoni schistosomula and adult worms with respect to purity, concentration, and yield. We tested the use of small (1.7 ml) iodixanol density gradients and demonstrated that this enabled western blot-based analysis of the EV marker protein tetraspanin-2 (TSP-2) in gradient fractions without additional concentration steps. Moreover, the concentration and yield of EVs obtained with small iodixanol gradients were higher compared to medium-sized (4.3 ml) or conventional large-sized (12 ml) gradients. Additionally, we provide evidence that iodixanol is preferred over sucrose as medium for the small density gradients, because EVs in iodixanol gradients reached equilibrium much faster (2 hours) and iodixanol but not sucrose was suitable for purification of schistosomula EVs. Finally, we demonstrate that the small iodixanol gradients were able to separate adult worm EVs from non-EV contaminants such as the blood digestion product hemozoin. Our optimized small iodixanol density gradient allows to simultaneously separate and concentrate EVs while reducing handling time and EV loss and can be applied for EVs from helminths and other limited EV sources. [ABSTRACT FROM AUTHOR]

Published
2022
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27. Excretion patterns of Schistosoma mansoni antigens CCA and CAA by adult male and female worms, using a mouse model and ex vivo parasite cultures.

Author

Casacuberta-Partal, Miriam, van Lieshout, Lisette, van Diepen, Angela, Sijtsma, Jeroen C., Ozir-Fazalalikhan, Arifa, Koopman, Jan Pieter R., de Dood, Claudia J., Corstjens, Paul L.A.M., van Dam, Govert J., Hokke, Cornelis H., and Roestenberg, Meta

Subjects
SCHISTOSOMA mansoni, LABORATORY mice, EXCRETION, ANIMAL disease models, WORMS
Abstract

Assays which enable the detection of schistosome gut-associated circulating anodic (CAA) and cathodic (CCA) antigen in serum or urine are increasingly used as a diagnostic tool for schistosome infection. However, little is known about the production and clearance of these circulating antigens in relation to the sex and reproductive maturity of the parasite. Here we describe CAA and CCA excretion patterns by exploring a mouse model after exposure to 36 male-only, female-only and mixed (male/female) Schistosoma mansoni cercariae. We found that serum and urine CAA levels, analysed at 3 weeks intervals, peaked at 6 weeks post-infection. Worms recovered after perfusion at 14 weeks were cultured ex vivo. Male parasites excreted more circulating antigens than females, in the mouse model as well as ex vivo. In mixed infections (supporting egg production), serum CAA levels correlated to the number of recovered worms, whereas faecal egg counts or Schistosoma DNA in stool did not. No viable eggs and no inflammation were seen in the livers from mice infected with female worms only. Ex vivo, CAA levels were higher than CCA levels. Our study confirms that CAA levels reflect worm burden and allows detection of low-level single-sex infections. [ABSTRACT FROM AUTHOR]

Published
2022
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28. Mass Spectrometric and Glycan Microarray–Based Characterization of the Filarial Nematode Brugia malayiGlycome Reveals Anionic and Zwitterionic Glycan Antigens

Author

Petralia, Laudine M.C., van Diepen, Angela, Lokker, Lena A., Nguyen, D. Linh, Sartono, Erliyani, Khatri, Vishal, Kalyanasundaram, Ramaswamy, Taron, Christopher H., Foster, Jeremy M., and Hokke, Cornelis H.

Abstract

Millions of people worldwide are infected with filarial nematodes, responsible for lymphatic filariasis (LF) and other diseases causing chronic disablement. Elimination programs have resulted in a substantial reduction of the rate of infection in certain areas creating a need for improved diagnostic tools to establish robust population surveillance and avoid LF resurgence. Glycans from parasitic helminths are emerging as potential antigens for use in diagnostic assays. However, despite its crucial role in host–parasite interactions, filarial glycosylation is still largely, structurally, and functionally uncharacterized. Therefore, we investigated the glycan repertoire of the filarial nematode Brugia malayi. Glycosphingolipid and N-linked glycans were extracted from several life-stages using enzymatic release and characterized using a combination of MALDI-TOF-MS and glycan sequencing techniques. Next, glycans were purified by HPLC and printed onto microarrays to assess the host anti-glycan antibody response. Comprehensive glycomic analysis of B. malayirevealed the presence of several putative antigenic motifs such as phosphorylcholine and terminal glucuronic acid. Glycan microarray screening showed a recognition of most B. malayiglycans by immunoglobulins from rhesus macaques at different time points after infection, which permitted the characterization of the dynamics of anti-glycan immunoglobulin G and M during the establishment of brugian filariasis. A significant level of IgG binding to the parasite glycans was also detected in infected human plasma, while IgG binding to glycans decreased after anthelmintic treatment. Altogether, our work identifies B. malayiglycan antigens and reveals antibody responses from the host that could be exploited as potential markers for LF.

Published
2022
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