TY - JOUR
T1 - Plasmodium sporozoites induce regulatory macrophages
AU - Winkel, B. atrice M. F.
AU - Pelgrom, Leonard R.
AU - van Schuijlenburg, Roos
AU - Baalbergen, Els
AU - Ganesh, Munisha S.
AU - Gerritsma, Heleen
AU - de Korne, Clarize M.
AU - Duszenko, Nikolas
AU - Langenberg, Marijke C. C.
AU - Chevalley-Maurel, S. verine C.
AU - Smits, Hermelijn H.
AU - de Jong, Esther C.
AU - Everts, Bart
AU - Franke-Fayard, Blandine
AU - Roestenberg, Meta
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85091324521&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.ppat.1008799
DO - https://doi.org/10.1371/journal.ppat.1008799
M3 - Article
C2 - 32898164
SN - 1553-7366
VL - 16
SP - e1008799
JO - PLoS pathogens
JF - PLoS pathogens
IS - 9
M1 - e1008799
ER -