Please use this identifier to cite or link to this item: http://docs.prosentient.com.au/prosentientjspui/handle/1/10848
Title: Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation.
Authors: Loughland, Jessica R
Minigo, Gabriela
Sarovich, Derek S
Field, Matt
Tipping, Peta E
Montes de Oca, Marcela
Piera, Kim A
Amante, Fiona H
Barber, Bridget E
Grigg, Matthew J
William, Timothy
Good, Michael F
Doolan, Denise L
Engwerda, Christian R
Anstey, Nicholas M
McCarthy, James S
Woodberry, Tonia
Affiliation: Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia. jessica.loughland@menzies.edu.au..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia.. Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sippy Downs, Queensland, Australia..
Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia.. Royal Darwin Hospital, Darwin, Australia..
QIMR Berghofer Medical Research Institute, Brisbane, Australia..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia..
QIMR Berghofer Medical Research Institute, Brisbane, Australia..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia.. Infectious Diseases Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia.. Infectious Diseases Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia..
Infectious Diseases Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia.. Sabah Department of Health, Kota Kinabalu, Sabah, Malaysia..
Griffith University, Gold Coast, Australia..
Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.. QIMR Berghofer Medical Research Institute, Brisbane, Australia..
QIMR Berghofer Medical Research Institute, Brisbane, Australia..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia.. Royal Darwin Hospital, Darwin, Australia..
QIMR Berghofer Medical Research Institute, Brisbane, Australia..
Menzies School of Health Research, Darwin, Australia and Charles Darwin University, Darwin, Australia..
Issue Date: 1-Jun-2017
Citation: Scientific reports 2017-06-01; 7(1): 2596
Abstract: 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 sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection.
URI: http://docs.prosentient.com.au/prosentientjspui/handle/1/10848
DOI: 10.1038/s41598-017-02096-2
Type: Journal Article
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