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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7fc57d1115ad4d4da48e9b4697978c9e
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spelling	oai:doaj.org-article:7fc57d1115ad4d4da48e9b4697978c9e2021-12-02T11:52:21ZPlasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation10.1038/s41598-017-02096-22045-2322https://doaj.org/article/7fc57d1115ad4d4da48e9b4697978c9e2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02096-2https://doaj.org/toc/2045-2322Abstract 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.Jessica R. LoughlandGabriela MinigoDerek S. SarovichMatt FieldPeta E. TippingMarcela Montes de OcaKim A. PieraFiona H. AmanteBridget E. BarberMatthew J. GriggTimothy WilliamMichael F. GoodDenise L. DoolanChristian R. EngwerdaNicholas M. AnsteyJames S. McCarthyTonia WoodberryNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
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 Portfolio
publishDate	2017
url	https://doaj.org/article/7fc57d1115ad4d4da48e9b4697978c9e
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Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

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