Journal Article

Plasmodium sporozoites induce regulatory macrophages

Winkel, Béatrice M. F., Langenberg, Marijke C. C., van Schuijlenburg, Roos, de Korne, Clarize M., Ganesh, Munisha S., Pelgrom, Leonard R., Duszenko, Nikolas, de Jong, Esther C., Roestenberg, Meta, Gerritsma, Heleen, Chevalley-Maurel, Séverine C., Everts, Bart, Franke-Fayard, Blandine, Baalbergen, Els, Smits, Hermelijn H.

2020

Overview

Professional antigen-presenting cells (APCs), like macrophages (M[PHI]s) 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 MoM[PHI]s. Both MoDCs and MoM[PHI]s readily took up recCSP but did not change phenotype or function upon doing so. SPZ are preferentially phagocytosed by MoM[PHI]s instead of DCs and phagocytosis greatly increased after opsonization. Subsequently MoM[PHI]s 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 (IFN[gamma]) production by antigen specific CD8.sup.+ 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antibodies / Antigen presenting cells / Antigens / Apoptosis / Biology and Life Sciences / CD8 antigen / Circumsporozoite protein / Dendritic cells / Development and progression / Drug delivery systems / Explants / Flow cytometry / Health aspects / Immunity / Immunity (Physiology) / Immunologic research / Immunology / Immunoregulation / Interferon / Interleukin / Interleukin 10 / Investigations / Laboratories / Lymphocytes / Lymphocytes T / Macrophages / Malaria / Malaria vaccines / Markers / Medicine and Health Sciences / Monocytes / Mosquitoes / Opsonization / Parasites / Parasitology / PD-L1 protein / Phagocytosis / Phenotypes / Physiological aspects / Plasmodium (Protozoa) / Proteins / Research and Analysis Methods / Sporozoites / Structure / Supervision / Surface markers / Vaccines / Vector-borne diseases / γ-Interferon