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Looking under the skin: the interaction between malaria parasites and the human skin

Projectomschrijving

Plasmodium falciparum malaria is een ernstige infectieziekte, overgedragen door muggen. In dit project is onderzocht hoe deze parasieten zich gedragen in de huid en hier
afweercellen beïnvloeden. Er werd een fluorescente tracer ontwikkeld waarmee malaria parasieten zichtbaar gemaakt kunnen worden en gevolgd kunnen worden in de menselijke
huid. Het blijkt dat malaria parasieten zich doelgericht bewegen, afhankelijk zijn van verschillende voedingsstoffen en dat door bestraling verzwakte parasieten zich anders
gaan gedragen. De malaria parasiet wordt wel opgemerkt door het menselijke afweersysteem, maar kan dit vervolgens onderdrukken. Andere parasieten zoals
bijvoorbeeld schistosoma doet dat ook op een zelfde manier. Het onderzoek richt zich nu op het onderzoeken van stoffen die het onderdrukken van het afweersysteem ongedaan
kunnen maken. Deze bevindingen zijn belangrijk om een effectief malariavaccin te kunnen ontwikkelen.

Producten

Titel: Establishing the Production of Male Schistosoma mansoni Cercariae for a Controlled Human Infection Model
Auteur: Janse, Jacqueline J, Langenberg, Marijke C C, Kos-Van Oosterhoud, Janneke, Ozir-Fazalalikhan, Arifa, Brienen, Eric A T, Winkel, Béatrice M F, Erkens, Marianne A A, van der Beek, Martha T, van Lieshout, Lisette, Smits, Hermelijn H, Webster, Bonnie L, Zandvliet, Maarten L, Verbeek, Richard, Westra, Inge M, Meij, Pauline, Visser, Leo G, van Diepen, Angela, Hokke, Cornelis H, Yazdanbakhsh, Maria, Roestenberg, Meta
Magazine: Journal of Infectious Diseases
Titel: Plasmodium falciparum Infection of Human Volunteers Activates Monocytes and CD16+Dendritic Cells and Induces Upregulation of CD16 and CD1c Expression
Auteur: Teirlinck, Anne C., Roestenberg, Meta, Bijker, Else M., Hoffman, Stephen L., Sauerwein, Robert W., Scholzen, Anja
Magazine: Infection and Immunity
Titel: Diagnosis and treatment based on quantitative PCR after controlled human malaria infection
Auteur: Walk, Jona, Schats, Remko, Langenberg, Marijke C. C., Reuling, Isaie J., Teelen, Karina, Roestenberg, Meta, Hermsen, Cornelus C., Visser, Leo G., Sauerwein, Robert W.
Magazine: Malaria Journal
Titel: Granulating wound after a holiday in Peru
Auteur: Vlasveld, I.N., Roestenberg, M., Visser, L.G.
Magazine: Netherlands Journal of Medicine
Link: http://www.njmonline.nl/getpdf.php?id=1914
Titel: Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection
Auteur: Obiero, Joshua M., Shekalaghe, Seif, Hermsen, Cornelus C., Mpina, Maxmillian, Bijker, Else M., Roestenberg, Meta, Teelen, Karina, Billingsley, Peter F., Sim, B. Kim Lee, James, Eric R., Daubenberger, Claudia A., Hoffman, Stephen L., Abdulla, Salim, Sauerwein, Robert W., Scholzen, Anja
Magazine: Infection and Immunity
Titel: Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites
Auteur: Marin-Mogollon, Catherin, van Pul, Fiona J. A., Miyazaki, Shinya, Imai, Takashi, Ramesar, Jai, Salman, Ahmed M., Winkel, Beatrice M. F., Othman, Ahmad Syibli, Kroeze, Hans, Chevalley-Maurel, Severine, Reyes-Sandoval, Arturo, Roestenberg, Meta, Franke-Fayard, Blandine, Janse, Chris J., Khan, Shahid M.
Magazine: Malaria Journal
Titel: Ethical and scientific considerations on the establishment of a controlled human infection model for schistosomiasis in Uganda: report of a stakeholders’ meeting held in Entebbe, Uganda. [version 2; referees: 2 approved]
Auteur: Alison M. Elliott, Meta Roestenberg, Anne Wajja, Christopher Opio, Francis Angumya, Moses Adriko, Moses Egesa, Serah Gitome, Joseph Mfutso-Bengo, Philip Bejon, Melissa Kapulu, Zoe Seager, Tom Lutalo, Winfred Badanga Nazziwa, Asuman Muwumuza, Maria Yazdanbakhsh, Pontiano Kaleebu, Narcis Kabatereine, Edridah Tukahebwa
Magazine: AAS Open Research
Titel: Clinical consequences of new diagnostic tools for intestinal parasites
Auteur: van Lieshout, L., Roestenberg, M.
Magazine: Clinical Microbiology and Infection
Titel: Repeated doses of Praziquantel in Schistosomiasis Treatment (RePST) – single versus multiple praziquantel treatments in school-aged children in Côte d’Ivoire: a study protocol for an open-label, randomised controlled trial
Auteur: Hoekstra, P. T., Casacuberta Partal, M., Amoah, A. S., van Lieshout, L., Corstjens, P. L. A. M., Tsonaka, S., Assaré, R. K., Silué, K. D., Meité, A., N’Goran, E. K., N’Gbesso, Y. K., Roestenberg, M., Knopp, S., Utzinger, J., Coulibaly, J. T., van Dam, G. J.
Magazine: BMC Infectious Diseases
Titel: In vivo stability of supramolecular host–guest complexes monitored by dual-isotope multiplexing in a pre-targeting model of experimental liver radioembolization
Auteur: Welling, Mick M., Spa, Silvia J., van Willigen, Danny M., Rietbergen, Daphne D.D., Roestenberg, Meta, Buckle, Tessa, van Leeuwen, Fijs W.B.
Magazine: Journal of Controlled Release
Link: https://www.sciencedirect.com/science/article/pii/S0168365918306667?via%3Dihub
Titel: Protective immunity differs between routes of administration of attenuated malaria parasites independent of parasite liver load
Auteur: Haeberlein, Simone, Chevalley-Maurel, Séverine, Ozir-Fazalalikhan, Arifa, Koppejan, Hester, Winkel, Beatrice M. F., Ramesar, Jai, Khan, Shahid M., Sauerwein, Robert W., Roestenberg, Meta, Janse, Chris J., Smits, Hermelijn H., Franke-Fayard, Blandine
Magazine: Scientific Reports
Titel: Katayama Syndrome Without Schistosoma mansoni Eggs
Auteur: Langenberg, Marijke C.C., Hoogerwerf, Marie-Astrid, Janse, Jacqueline J., van Lieshout, Lisette, Corstjens, Paul L.A.M., Roestenberg, Meta
Magazine: Annals of Internal Medicine
Titel: The frontline of controlled human malaria infections: A report from the controlled human infection models Workshop in Leiden University Medical Centre 5 May 2016
Auteur: Roestenberg, Meta, Mordmüller, Benjamin, Ockenhouse, Chris, Mo, Annie, Yazdanbakhsh, Maria, Kremsner, Peter G.
Magazine: Vaccine
Titel: Early Induction of Human Regulatory Dermal Antigen Presenting Cells by Skin-Penetrating Schistosoma Mansoni Cercariae
Auteur: Winkel, Béatrice M. F., Dalenberg, Mirjam R., de Korne, Clarize M., Feijt, Carola, Langenberg, Marijke C. C., Pelgrom, Leonard, Ganesh, Munisha S., Yazdanbakhsh, Maria, Smits, Hermelijn Helene, de Jong, Esther C., Everts, Bart, van Leeuwen, Fijs W. B., Hokke, Cornelis H., Roestenberg, Meta
Magazine: Frontiers in Immunology
Titel: A framework for Controlled Human Infection Model (CHIM) studies in Malawi: Report of a Wellcome Trust workshop on CHIM in Low Income Countries held in Blantyre, Malawi
Auteur: Gordon, Stephen B, Rylance, Jamie, Luck, Amy, Jambo, Kondwani, Ferreira, Daniela M, Manda-Taylor, Lucinda, Bejon, Philip, Ngwira, Bagrey, Littler, Katherine, Seager, Zoe, Gibani, Malick, Gmeiner, Markus, Roestenberg, Meta, Mlombe, Yohannie
Magazine: Wellcome open resource
Titel: Experimental infection of human volunteers
Auteur: Roestenberg, Meta, Hoogerwerf, Marie-Astrid, Ferreira, Daniela M, Mordmüller, Benjamin, Yazdanbakhsh, Maria
Magazine: Lancet Infectious Diseases
Link: https://www.sciencedirect.com/science/article/pii/S1473309918301774?via%3Dihub
Titel: Controlled Human Infections As a Tool to Reduce Uncertainty in Clinical Vaccine Development
Auteur: Roestenberg, Meta, Kamerling, Ingrid M. C., de Visser, Saco J.
Magazine: Frontiers in Medicine
Titel: Controlled human infections: A report from the controlled human infection models workshop, Leiden University Medical Centre 4-6 May 2016.
Auteur: Roestenberg, Meta, Mo, Annie, Kremsner, Peter G., Yazdanbakhsh, Maria
Magazine: Vaccine

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Samenvatting van de aanvraag

Plasmodium falciparum (Pf) malaria is one of the most devastating infectious diseases worldwide. A highly efficacious malaria vaccine is urgently needed, but subunit vaccines provide only modest protection. Long-lasting sterile protection can be induced by immunization with live, attenuated parasites through the bite of infected mosquitoes and requires malaria-specific T-cells. With technical advances in purifying and cryopreserving these parasites, the field of attenuated-parasite (AP) vaccination is rapidly evolving. Unfortunately, the first clinical trial with an AP vaccine lacked efficacy, because needle injection compromised parasite migration and immunogenicity as compared to mosquito bites. These observations emphasize the need to fully comprehend the role of skin in infection and protection to malaria. Little is known about the physiology of malaria parasites in human skin. Skin-patrolling dendritic cells (DCs) are proposed to prime regional lymph node T-cells, resulting in effector, cytotoxic or tolerogenic responses. Intriguingly, contradicting conventional beliefs, rodent malaria parasites can persist in the skin for weeks, where they could manipulate the T-cell priming abilities of various types of DCs. The interactions of human malaria parasites within the skin are largely unexplored, but crucial to understanding AP vaccination. Here, I propose to fill this knowledge gap, hypothesizing that human skin stage parasites modulate local immune cells including skin DCs, thereby shaping regional lymph node responses, allowing immune evasion and escape of parasites and ultimately deactivating systemic anti-malarial immunity. In this grant proposal, I aim to (a) characterize Pf parasite development in human skin, (b) examine the functional properties of human skin DCs upon interaction with Pf parasites and (c) determine the effect of parasite attenuation, injection mode and adjuvants on skin DCs. A well-established controlled human malaria infection model will be used to generate in vivo data. These studies readily contribute to the development of an efficacious attenuated parasite malaria vaccine.

Onderwerpen

Kenmerken

Projectnummer:
91615076
Looptijd: 100%
Looptijd: 100 %
2014
2018
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Dr. M. Roestenberg
Verantwoordelijke organisatie:
Leiden University Medical Center