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

doi:10.1093/infdis/jiy555

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

Global and Tropical Health

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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 language	English
Article number	jiy555
Pages (from-to)	660-671
Number of pages	12
Journal	The Journal of infectious diseases
Volume	219
Issue number	4
Early online date	15 Oct 2018
DOIs	https://doi.org/10.1093/infdis/jiy555
Publication status	Published - 29 Jan 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/infdis/jiy555Licence: CC BY

Cite this

Loughland, J. R., Woodberry, T., Boyle, M. J., Tipping, P. E., Piera, K. A., Amante, F. H., Kenangalem, E., Price, R. N., Engwerda, C. R., Anstey, N. M., McCarthy, J. S., & 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, 219(4), 660-671. Article jiy555. https://doi.org/10.1093/infdis/jiy555

@article{6e4158486cb94ae7bb7ab12369cc9de3,

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

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",

year = "2019",

month = jan,

day = "29",

doi = "10.1093/infdis/jiy555",

language = "English",

volume = "219",

pages = "660--671",

journal = "The Journal of infectious diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "4",

}

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, jiy555, pp. 660-671. https://doi.org/10.1093/infdis/jiy555

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=85058717906&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiy555

DO - 10.1093/infdis/jiy555

M3 - Article

C2 - 30239833

SN - 0022-1899

VL - 219

SP - 660

EP - 671

JO - The Journal of infectious diseases

JF - The Journal of infectious diseases

IS - 4

M1 - jiy555

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this