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

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    Author(s)
    de Oca, Marcela Montes
    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
    Griffith University Author(s)
    Ng, Susanna SS.
    Bunn, Patrick
    Engwerda, Christian R.
    Boyle, Glen M.
    Year published
    2016
    Metadata
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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 ...
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    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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    Journal Title
    Cell Reports
    Volume
    17
    Issue
    2
    DOI
    https://doi.org/10.1016/j.celrep.2016.09.015
    Copyright Statement
    © 2016 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
    Subject
    Biochemistry and cell biology
    Biochemistry and cell biology not elsewhere classified
    Medical physiology
    Publication URI
    http://hdl.handle.net/10072/124046
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    • Journal articles

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