Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

J R Loughland; G Minigo; Derek S Sarovich; M Field; P E Tipping; M M de Oca; K A Piera; F H Amante; B E Barber; M J Grigg; T William; M F Good; D L Doolan; C R Engwerda; N M Anstey; J S McCarthy; T Woodberry

doi:10.1038/s41598-017-02096-2

Back

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

Journal article

Open access

Peer reviewed

Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

J R Loughland, G Minigo, Derek S Sarovich, M Field, P E Tipping, M M de Oca, K A Piera, F H Amante, B E Barber, M J Grigg, …

Scientific Reports, Vol.7(2596)

2017

DOI: https://doi.org/10.1038/s41598-017-02096-2

Files and links (2)

pdf

PDF - Published Version (Open Access)2.07 MBDownload View

Published VersionPDF - Published Version (Open Access)CC BY V4.0, Open Access

url

https://doi.org/10.1038/s41598-017-02096-2View

Published Version

Abstract

Biochemistry and Cell Biology

Other Physical Sciences

plasmodium parasites

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR <0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite submicroscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection.

Details

Title: Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation
Authors: J R Loughland (Author) - Menzies School of Health Research
G Minigo (Author) - Menzies School of Health Research
Derek S Sarovich (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
M Field (Author) - James Cook University
P E Tipping (Author) - Menzies School of Health Research
M M de Oca (Author) - QIMR Berghofer Medical Research Institute
K A Piera (Author) - Menzies School of Health Research
F H Amante (Author) - QIMR Berghofer Medical Research Institute
B E Barber (Author) - Menzies School of Health Research
M J Grigg (Author) - Menzies School of Health Research
T William (Author) - Kota Kinabalu, Malaysia
M F Good (Author) - Griffith University
D L Doolan (Author) - James Cook University
C R Engwerda (Author) - QIMR Berghofer Medical Research Institute
N M Anstey (Author) - Menzies School of Health Research
J S McCarthy (Author) - QIMR Berghofer Medical Research Institute
T Woodberry (Author) - Menzies School of Health Research
Publication details: Scientific Reports, Vol.7(2596); 11
Publisher: Nature Publishing Group
Date published: 2017
DOI: 10.1038/s41598-017-02096-2
ISSN: 2045-2322
Copyright note: Copyright © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Organisation Unit: UniSC Clinical Trials Centre; University of the Sunshine Coast, Queensland; Centre for Bioinnovation
Language: English
Record Identifier: 99451081902621
Output Type: Journal article

Metrics

85 File views/ downloads

577 Record Views

24 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Immunology

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites