Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria

Jessica R. Loughland, Tonia Woodberry, Michelle J. Boyle, Peta E. Tipping, Kim A. Piera, Fiona H. Amante, Enny Kenangalem, Ric N. Price, Christian R. Engwerda, Nicholas M. Anstey, James S. McCarthy, Gabriela Minigo

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs).

Methods: In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers.

Results: CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10. In vitro restimulation with P falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function.

Conclusions: These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.

Original languageEnglish
Pages (from-to)660-671
Number of pages12
JournalThe Journal of infectious diseases
Volume219
Issue number4
Early online date15 Oct 2018
DOIs
Publication statusPublished - 29 Jan 2019

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Plasmodium falciparum
Interleukin-10
Dendritic Cells
Malaria
Tumor Necrosis Factor-alpha
Cytokines
Parasites
Plasmodium
Toll-Like Receptors
HLA Antigens
Ligation
Volunteers
Infection

Cite this

Loughland, Jessica R. ; Woodberry, Tonia ; Boyle, Michelle J. ; Tipping, Peta E. ; Piera, Kim A. ; Amante, Fiona H. ; Kenangalem, Enny ; Price, Ric N. ; Engwerda, Christian R. ; Anstey, Nicholas M. ; McCarthy, James S. ; Minigo, Gabriela. / Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria. In: The Journal of infectious diseases. 2019 ; Vol. 219, No. 4. pp. 660-671.
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abstract = "Background: The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs). Methods: In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers. Results: CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10. In vitro restimulation with P falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function. Conclusions: These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.",
author = "Loughland, {Jessica R.} and Tonia Woodberry and Boyle, {Michelle J.} and Tipping, {Peta E.} and Piera, {Kim A.} and Amante, {Fiona H.} and Enny Kenangalem and Price, {Ric N.} and Engwerda, {Christian R.} and Anstey, {Nicholas M.} and McCarthy, {James S.} and Gabriela Minigo",
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Loughland, JR, Woodberry, T, Boyle, MJ, Tipping, PE, Piera, KA, Amante, FH, Kenangalem, E, Price, RN, Engwerda, CR, Anstey, NM, McCarthy, JS & Minigo, G 2019, 'Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria' The Journal of infectious diseases, vol. 219, no. 4, pp. 660-671. https://doi.org/10.1093/infdis/jiy555

Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria. / Loughland, Jessica R.; Woodberry, Tonia; Boyle, Michelle J.; Tipping, Peta E.; Piera, Kim A.; Amante, Fiona H.; Kenangalem, Enny; Price, Ric N.; Engwerda, Christian R.; Anstey, Nicholas M.; McCarthy, James S.; Minigo, Gabriela.

In: The Journal of infectious diseases, Vol. 219, No. 4, 29.01.2019, p. 660-671.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Plasmodium falciparum Activates CD16+ Dendritic Cells to Produce Tumor Necrosis Factor and Interleukin-10 in Subpatent Malaria

AU - Loughland, Jessica R.

AU - Woodberry, Tonia

AU - Boyle, Michelle J.

AU - Tipping, Peta E.

AU - Piera, Kim A.

AU - Amante, Fiona H.

AU - Kenangalem, Enny

AU - Price, Ric N.

AU - Engwerda, Christian R.

AU - Anstey, Nicholas M.

AU - McCarthy, James S.

AU - Minigo, Gabriela

PY - 2019/1/29

Y1 - 2019/1/29

N2 - Background: The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs). Methods: In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers. Results: CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10. In vitro restimulation with P falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function. Conclusions: These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.

AB - Background: The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs). Methods: In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers. Results: CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10. In vitro restimulation with P falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function. Conclusions: These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.

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DO - 10.1093/infdis/jiy555

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JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

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