Plasmodium sporozoites induce regulatory macrophages
| العنوان: | Plasmodium sporozoites induce regulatory macrophages |
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| المؤلفون: | Blandine Franke-Fayard, Munisha S. Ganesh, Meta Roestenberg, Hermelijn H. Smits, Nikolas Duszenko, Severine Chevalley-Maurel, Roos van Schuijlenburg, Bart Everts, Heleen Gerritsma, Els Baalbergen, Marijke C. C. Langenberg, Clarize M. de Korne, Leonard R. Pelgrom, Esther C. de Jong, Beatrice M. F. Winkel |
| المساهمون: | Experimental Immunology, AII - Inflammatory diseases |
| المصدر: | PLoS Pathogens, Vol 16, Iss 9, p e1008799 (2020) PLoS Pathogens, 16(9). PUBLIC LIBRARY SCIENCE PLoS Pathogens PLoS pathogens, 16(9):e1008799. Public Library of Science |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Plasmodium berghei, Protozoan Proteins, Regulatory macrophages, White Blood Cells, Mice, Medical Conditions, Spectrum Analysis Techniques, Animal Cells, Medicine and Health Sciences, Cytotoxic T cell, Interferon gamma, Biology (General), Cells, Cultured, Skin, Protozoans, 0303 health sciences, T Cells, 030302 biochemistry & molecular biology, Malarial Parasites, Eukaryota, Flow Cytometry, Interleukin 10, Spectrophotometry, Sporozoites, Female, Cytophotometry, Cellular Types, Anatomy, Integumentary System, medicine.drug, Research Article, QH301-705.5, Immune Cells, Immunology, Antigen-Presenting Cells, Cytotoxic T cells, Biology, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Immunity, Virology, Genetics, medicine, Parasitic Diseases, Animals, Humans, Antigen-presenting cell, Molecular Biology, 030304 developmental biology, Innate immune system, Blood Cells, Macrophages, Organisms, Biology and Life Sciences, Cell Biology, RC581-607, Tropical Diseases, Parasitic Protozoans, Malaria, Parasitology, Immunologic diseases. Allergy, CD8 |
| الوصف: | Professional antigen-presenting cells (APCs), like macrophages (Mϕs) and dendritic cells (DCs), are central players in the induction of natural and vaccine-induced immunity to malaria, yet very little is known about the interaction of SPZ with human APCs. Intradermal delivery of whole-sporozoite vaccines reduces their effectivity, possibly due to dermal immunoregulatory effects. Therefore, understanding these interactions could prove pivotal to malaria vaccination. We investigated human APC responses to recombinant circumsporozoite protein (recCSP), SPZ and anti-CSP opsonized SPZ both in monocyte derived MoDCs and MoMϕs. Both MoDCs and MoMϕs readily took up recCSP but did not change phenotype or function upon doing so. SPZ are preferentially phagocytosed by MoMϕs instead of DCs and phagocytosis greatly increased after opsonization. Subsequently MoMϕs show increased surface marker expression of activation markers as well as tolerogenic markers such as Programmed Death-Ligand 1 (PD-L1). Additionally they show reduced motility, produce interleukin 10 and suppressed interferon gamma (IFNγ) production by antigen specific CD8+ T cells. Importantly, we investigated phenotypic responses to SPZ in primary dermal APCs isolated from human skin explants, which respond similarly to their monocyte-derived counterparts. These findings are a first step in enhancing our understanding of pre-erythrocytic natural immunity and the pitfalls of intradermal vaccination-induced immunity. Author summary Malaria continues to be the deadliest parasitic disease worldwide, and an effective vaccine yielding sterile immunity does not yet exist. Attenuated parasites can induce sterile protection in both human and rodent models for malaria, but these vaccines need to be administered directly into the bloodstream in order to convey protection; administration via the skin results in a much-reduced efficacy. We hypothesized this is caused by an early immune regulation initiated at the first site of contact with the immune system: the skin. However, the human skin stage of malaria has not been investigated to date. We used human antigen presenting cells as well as whole human skin explants to investigate (dermal) immune responses and found that Plasmodium sporozoites are able to suppress immune responses by inducing regulatory macrophages. Our study provides new insights in the mechanism of early immune regulation exploited by Plasmodium parasites and can help to explain why intradermal vaccination using whole attenuated sporozoites results in reduced protection. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1553-7366 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd25234b202e95a20002439405b6ce03 http://www.scopus.com/inward/record.url?scp=85091324521&partnerID=8YFLogxK |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bd25234b202e95a20002439405b6ce03 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537366 |
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