Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria

J. R. Loughland, T. Woodberry, M. J. Boyle, P. E. Tipping, K. A. Piera, F. H. Amante, E. Kenangalem, R. N. Price, C. R. Engwerda, N. M. Anstey, J. S. McCarthy, G. Minigo

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: The malaria causing parasite Plasmodium subverts host immuneresponses 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 under went 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 Pfalciparum 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
    Article numberjiy555
    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

    Fingerprint

    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, J. R., Woodberry, T., Boyle, M. J., Tipping, P. E., Piera, K. A., Amante, F. H., ... Minigo, G. (2019). Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria. The Journal of infectious diseases, 219(4), 660-671. [jiy555]. https://doi.org/10.1093/infdis/jiy555
    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. / Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria. In: The Journal of infectious diseases. 2019 ; Vol. 219, No. 4. pp. 660-671.
    @article{6e4158486cb94ae7bb7ab12369cc9de3,
    title = "Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria",
    abstract = "Background: The malaria causing parasite Plasmodium subverts host immuneresponses 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 under went 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 Pfalciparum 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, {J. R.} and T. Woodberry and Boyle, {M. J.} and Tipping, {P. E.} and Piera, {K. A.} and Amante, {F. H.} and E. Kenangalem and Price, {R. N.} and Engwerda, {C. R.} and Anstey, {N. M.} and McCarthy, {J. S.} and G. 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 TNF and IL-10 in subpatent malaria', The Journal of infectious diseases, vol. 219, no. 4, jiy555, pp. 660-671. https://doi.org/10.1093/infdis/jiy555

    Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria. / 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.

    In: The Journal of infectious diseases, Vol. 219, No. 4, jiy555, 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 TNF and IL-10 in subpatent malaria

    AU - Loughland, J. R.

    AU - Woodberry, T.

    AU - Boyle, M. J.

    AU - Tipping, P. E.

    AU - Piera, K. A.

    AU - Amante, F. H.

    AU - Kenangalem, E.

    AU - Price, R. N.

    AU - Engwerda, C. R.

    AU - Anstey, N. M.

    AU - McCarthy, J. S.

    AU - Minigo, G.

    PY - 2019/1/29

    Y1 - 2019/1/29

    N2 - Background: The malaria causing parasite Plasmodium subverts host immuneresponses 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 under went 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 Pfalciparum 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 immuneresponses 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 under went 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 Pfalciparum 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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    Loughland JR, Woodberry T, Boyle MJ, Tipping PE, Piera KA, Amante FH et al. Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in subpatent malaria. The Journal of infectious diseases. 2019 Jan 29;219(4):660-671. jiy555. https://doi.org/10.1093/infdis/jiy555