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  • Early Changes in CD4(+) T-Cell Activation During Blood-Stage Plasmodium falciparum Infection

    Author(s)
    Edwards, Chelsea L
    Ng, Susanna S
    Corvino, Dillon
    de Oca, Marcela Montes
    Rivera, Fabian de labastida
    Nones, Katia
    Lakis, Vanessa
    Waddell, Nicola
    Amante, Fiona H
    McCarthy, James S
    Engwerda, Christian R
    Griffith University Author(s)
    Engwerda, Christian R.
    Ng, Susanna SS.
    Year published
    2018
    Metadata
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    Abstract
    We examined transcriptional changes in CD4+ T cells during blood-stage Plasmodium falciparum infection in individuals without a history of previous parasite exposure. Transcription of CXCL8 (encoding interleukin 8) in CD4+ T cells was identified as an early biomarker of submicroscopic P. falciparum infection, with predictive power for parasite growth. Following antiparasitic drug treatment, a CD4+ T-cell regulatory phenotype developed. PD1 expression on CD49b+CD4+ T (putative type I regulatory T) cells after drug treatment negatively correlated with earlier parasite growth. Blockade of PD1 but no other immune checkpoint ...
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    We examined transcriptional changes in CD4+ T cells during blood-stage Plasmodium falciparum infection in individuals without a history of previous parasite exposure. Transcription of CXCL8 (encoding interleukin 8) in CD4+ T cells was identified as an early biomarker of submicroscopic P. falciparum infection, with predictive power for parasite growth. Following antiparasitic drug treatment, a CD4+ T-cell regulatory phenotype developed. PD1 expression on CD49b+CD4+ T (putative type I regulatory T) cells after drug treatment negatively correlated with earlier parasite growth. Blockade of PD1 but no other immune checkpoint molecules tested increased interferon γ and interleukin 10 production in an ex vivo antigen-specific cellular assay at the peak of infection. These results demonstrate the early development of an immunoregulatory CD4+ T-cell phenotype in blood-stage P. falciparum infection and show that a selective immune checkpoint blockade may be used to modulate early developing antiparasitic immunoregulatory pathways as part of malaria vaccine and/or drug treatment protocols.
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    Journal Title
    JOURNAL OF INFECTIOUS DISEASES
    Volume
    218
    Issue
    7
    DOI
    https://doi.org/10.1093/infdis/jiy281
    Subject
    Biological sciences
    Biomedical and clinical sciences
    Publication URI
    http://hdl.handle.net/10072/383753
    Collection
    • Journal articles

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