Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection

Marcela Montes de Oca, Rajiv Kumar, Fabian de Labastida Rivera, Fiona H. Amante, Meru Sheel, Rebecca J. Faleiro, Patrick T. Bunn, Shannon E. Best, Lynette Beattie, Susanna S. Ng, Chelsea L. Edwards, Glen M. Boyle, Ric N. Price, Nicholas M. Anstey, Jessica R. Loughland, Julie Burel, Denise L. Doolan, Ashraful Haque, James S. McCarthy, Christian R. Engwerda

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    Abstract

    The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement.

    Original languageEnglish
    Pages (from-to)399-412
    Number of pages14
    JournalCell Reports
    Volume17
    Issue number2
    DOIs
    Publication statusPublished - 4 Oct 2016

    Fingerprint

    Interferon Type I
    Plasmodium falciparum
    Interleukin-10
    Malaria
    Blood
    Parasites
    Vaccines
    Drug therapy
    Active Immunotherapy
    Th1 Cells
    Falciparum Malaria
    Chemoprevention
    Pathogens
    Regulatory T-Lymphocytes
    Pharmaceutical Preparations
    Interferons
    Immunity
    Healthy Volunteers
    Cytokines
    Infection

    Cite this

    Montes de Oca, M., Kumar, R., Rivera, F. D. L., Amante, F. H., Sheel, M., Faleiro, R. J., ... Engwerda, C. R. (2016). Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection. Cell Reports, 17(2), 399-412. https://doi.org/10.1016/j.celrep.2016.09.015
    Montes de Oca, Marcela ; Kumar, Rajiv ; Rivera, Fabian de Labastida ; Amante, Fiona H. ; Sheel, Meru ; Faleiro, Rebecca J. ; Bunn, Patrick T. ; Best, Shannon E. ; Beattie, Lynette ; Ng, Susanna S. ; Edwards, Chelsea L. ; Boyle, Glen M. ; Price, Ric N. ; Anstey, Nicholas M. ; Loughland, Jessica R. ; Burel, Julie ; Doolan, Denise L. ; Haque, Ashraful ; McCarthy, James S. ; Engwerda, Christian R. / Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection. In: Cell Reports. 2016 ; Vol. 17, No. 2. pp. 399-412.
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    abstract = "The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement.",
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    Montes de Oca, M, Kumar, R, Rivera, FDL, Amante, FH, Sheel, M, Faleiro, RJ, Bunn, PT, Best, SE, Beattie, L, Ng, SS, Edwards, CL, Boyle, GM, Price, RN, Anstey, NM, Loughland, JR, Burel, J, Doolan, DL, Haque, A, McCarthy, JS & Engwerda, CR 2016, 'Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection', Cell Reports, vol. 17, no. 2, pp. 399-412. https://doi.org/10.1016/j.celrep.2016.09.015

    Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection. / Montes de Oca, Marcela; Kumar, Rajiv; Rivera, Fabian de Labastida; Amante, Fiona H.; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Boyle, Glen M.; Price, Ric N.; Anstey, Nicholas M.; Loughland, Jessica R.; Burel, Julie; Doolan, Denise L.; Haque, Ashraful; McCarthy, James S.; Engwerda, Christian R.

    In: Cell Reports, Vol. 17, No. 2, 04.10.2016, p. 399-412.

    Research output: Contribution to journalArticleResearchpeer-review

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    AU - Amante, Fiona H.

    AU - Sheel, Meru

    AU - Faleiro, Rebecca J.

    AU - Bunn, Patrick T.

    AU - Best, Shannon E.

    AU - Beattie, Lynette

    AU - Ng, Susanna S.

    AU - Edwards, Chelsea L.

    AU - Boyle, Glen M.

    AU - Price, Ric N.

    AU - Anstey, Nicholas M.

    AU - Loughland, Jessica R.

    AU - Burel, Julie

    AU - Doolan, Denise L.

    AU - Haque, Ashraful

    AU - McCarthy, James S.

    AU - Engwerda, Christian R.

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    N2 - The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement.

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    KW - malaria

    KW - Th1 cells

    KW - Tr1 cells

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    Montes de Oca M, Kumar R, Rivera FDL, Amante FH, Sheel M, Faleiro RJ et al. Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection. Cell Reports. 2016 Oct 4;17(2):399-412. https://doi.org/10.1016/j.celrep.2016.09.015