10.3389/fimmu.2018.02510.s002
Béatrice M. F. Winkel
Béatrice M. F.
Winkel
Mirjam R. Dalenberg
Mirjam R.
Dalenberg
Clarize M. de Korne
Clarize M.
de Korne
Carola Feijt
Carola
Feijt
Marijke C. C. Langenberg
Marijke C. C.
Langenberg
Leonard Pelgrom
Leonard
Pelgrom
Munisha S. Ganesh
Munisha S.
Ganesh
Maria Yazdanbakhsh
Maria
Yazdanbakhsh
Hermelijn Helene Smits
Hermelijn Helene
Smits
Esther C. de Jong
Esther
C. de Jong
Bart Everts
Bart
Everts
Fijs W. B. van Leeuwen
Fijs
W. B. van Leeuwen
Cornelis H. Hokke
Cornelis H.
Hokke
Meta Roestenberg
Meta
Roestenberg
Video_1_Early Induction of Human Regulatory Dermal Antigen Presenting Cells by Skin-Penetrating Schistosoma Mansoni Cercariae.MP4
Frontiers
2018
schistosome
Schistosoma mansoni
cercaria
bilharzia
human
skin
macrophage
PD-L1
2018-10-31 13:47:34
Media
https://frontiersin.figshare.com/articles/media/Video_1_Early_Induction_of_Human_Regulatory_Dermal_Antigen_Presenting_Cells_by_Skin-Penetrating_Schistosoma_Mansoni_Cercariae_MP4/7276283
<p>Following initial invasion of Schistosoma mansoni cercariae, schistosomula reside in the skin for several days during which they can interact with the dermal immune system. While murine experiments have indicated that exposure to radiation-attenuated (RA) cercariae can generate protective immunity which is initiated in the skin stage, contrasting non-attenuated cercariae, such data is missing for the human model. Since murine skin does not form a reliable marker for immune responses in human skin, we used human skin explants to study the interaction with non-attenuated and RA cercariae with dermal innate antigen presenting cells (APCs) and the subsequent immunological responses. We exposed human skin explants to cercariae and visualized their invasion in real time (initial 30 min) using novel imaging technologies. Subsequently, we studied dermal immune responses and found an enhanced production of regulatory cytokine interleukin (IL)-10, pro-inflammatory cytokine IL-6 and macrophage inflammatory protein (MIP)-1α within 3 days of exposure. Analysis of dermal dendritic cells (DDCs) for their phenotype revealed an increased expression of immune modulators programmed death ligand (PD-L) 1 and 2, and increased IL-10 production. Ex vivo primed DDCs suppress Th1 polarization of naïve T-cells and increase T-cell IL-10 production, indicating their regulatory potential. These immune responses were absent or decreased after exposure to RA parasites. Using transwells, we show that direct contact between APCs and cercariae is required to induce their regulatory phenotype. To the best of our knowledge this is the first study that attempts to provide insight in the human dermal S. mansoni cercariae invasion and subsequent immune responses comparing non-attenuated with RA parasites. We reveal that cercariae induce a predominantly regulatory immune response whereas RA cercariae fail to achieve this. This initial understanding of the dermal immune suppressive capacity of S. mansoni cercariae in humans provides a first step toward the development of an effective schistosome vaccine.</p>