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  • Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria

    Author(s)
    Vijay, Rahul
    Guthmiller, Jenna J
    Sturtz, Alexandria J
    Surette, Fionna A
    Rogers, Kai J
    Sompallae, Ramakrishna R
    Li, Fengyin
    Pope, Rosemary L
    Chan, Jo-Anne
    Rivera, Fabian de Labastida
    Andrew, Dean
    Webb, Lachlan
    Engwerda, Christian R
    Boyle, Michelle J
    et al.
    Griffith University Author(s)
    Engwerda, Christian R.
    Boyle, Michelle
    Year published
    2020
    Metadata
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    Abstract
    Plasmodium parasite-specific antibodies are critical for protection against malaria, yet the development of long-lived and effective humoral immunity against Plasmodium takes many years and multiple rounds of infection and cure. Here, we report that the rapid development of short-lived plasmablasts during experimental malaria unexpectedly hindered parasite control by impeding germinal center responses. Metabolic hyperactivity of plasmablasts resulted in nutrient deprivation of the germinal center reaction, limiting the generation of memory B cell and long-lived plasma cell responses. Therapeutic administration of a single ...
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    Plasmodium parasite-specific antibodies are critical for protection against malaria, yet the development of long-lived and effective humoral immunity against Plasmodium takes many years and multiple rounds of infection and cure. Here, we report that the rapid development of short-lived plasmablasts during experimental malaria unexpectedly hindered parasite control by impeding germinal center responses. Metabolic hyperactivity of plasmablasts resulted in nutrient deprivation of the germinal center reaction, limiting the generation of memory B cell and long-lived plasma cell responses. Therapeutic administration of a single amino acid to experimentally infected mice was sufficient to overcome the metabolic constraints imposed by plasmablasts and enhanced parasite clearance and the formation of protective humoral immune memory responses. Thus, our studies not only challenge the current model describing the role and function of blood-stage Plasmodium-induced plasmablasts but they also reveal new targets and strategies to improve anti-Plasmodium humoral immunity.
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    Journal Title
    Nature Immunology
    Volume
    21
    Issue
    7
    DOI
    https://doi.org/10.1038/s41590-020-0678-5
    Subject
    Immunology
    Science & Technology
    Life Sciences & Biomedicine
    MEMORY B-CELLS
    BLOOD-STAGE MALARIA
    Publication URI
    http://hdl.handle.net/10072/396527
    Collection
    • Journal articles

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