Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation
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...
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doaj-7fc57d1115ad4d4da48e9b4697978c9e2020-12-08T00:39:02ZengNature Publishing GroupScientific Reports2045-23222017-06-017111110.1038/s41598-017-02096-2Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulationJessica R. Loughland0Gabriela Minigo1Derek S. Sarovich2Matt Field3Peta E. Tipping4Marcela Montes de Oca5Kim A. Piera6Fiona H. Amante7Bridget E. Barber8Matthew J. Grigg9Timothy William10Michael F. Good11Denise L. Doolan12Christian R. Engwerda13Nicholas M. Anstey14James S. McCarthy15Tonia Woodberry16Menzies School of Health Research, Darwin, Australia and Charles Darwin UniversityMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityAustralian Institute of Tropical Health and Medicine, James Cook UniversityMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityQIMR Berghofer Medical Research InstituteMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityQIMR Berghofer Medical Research InstituteMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityInfectious Diseases Unit, Queen Elizabeth HospitalGriffith UniversityAustralian Institute of Tropical Health and Medicine, James Cook UniversityQIMR Berghofer Medical Research InstituteMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityQIMR Berghofer Medical Research InstituteMenzies School of Health Research, Darwin, Australia and Charles Darwin UniversityAbstract 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.https://doi.org/10.1038/s41598-017-02096-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jessica R. Loughland Gabriela Minigo Derek S. Sarovich Matt Field Peta E. Tipping Marcela Montes de Oca Kim A. Piera Fiona H. Amante Bridget E. Barber Matthew J. Grigg Timothy William Michael F. Good Denise L. Doolan Christian R. Engwerda Nicholas M. Anstey James S. McCarthy Tonia Woodberry |
spellingShingle |
Jessica R. Loughland Gabriela Minigo Derek S. Sarovich Matt Field Peta E. Tipping Marcela Montes de Oca Kim A. Piera Fiona H. Amante Bridget E. Barber Matthew J. Grigg Timothy William Michael F. Good Denise L. Doolan Christian R. Engwerda Nicholas M. Anstey James S. McCarthy Tonia Woodberry Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation Scientific Reports |
author_facet |
Jessica R. Loughland Gabriela Minigo Derek S. Sarovich Matt Field Peta E. Tipping Marcela Montes de Oca Kim A. Piera Fiona H. Amante Bridget E. Barber Matthew J. Grigg Timothy William Michael F. Good Denise L. Doolan Christian R. Engwerda Nicholas M. Anstey James S. McCarthy Tonia Woodberry |
author_sort |
Jessica R. Loughland |
title |
Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation |
title_short |
Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation |
title_full |
Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation |
title_fullStr |
Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation |
title_full_unstemmed |
Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation |
title_sort |
plasmacytoid dendritic cells appear inactive during sub-microscopic plasmodium falciparum blood-stage infection, yet retain their ability to respond to tlr stimulation |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-06-01 |
description |
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. |
url |
https://doi.org/10.1038/s41598-017-02096-2 |
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