Low-Level Plasmodium falciparum Blood-Stage Infection Causes Dendritic Cell Apoptosis and Dysfunction in Healthy Volunteers

Tonia Woodberry, Gabriela Minigo, Kim Piera, Fiona Amante, A PINZON-CHARRY, M GOOD, Alejandro Lopez, Christian Engwerda, James McCarthy, Nicholas Anstey

    Research output: Contribution to journalArticle

    Abstract

    Background: Dendritic cells (DCs) are highly specialized antigen-presenting cells that are crucial for initiation of immune responses. During naturally acquired malaria, DC number and function is reduced.

     

    Methods: The timing of, parasitemia threshold of, and contribution of apoptosis to DC loss were prospectively evaluated in 10 men after experimental challenge with approximately 1800 Plasmodium falciparum–parasitized red blood cells (pRBCs) and after drug cure initiated at a parasite level of ≥1000 parasites/mL.

     

    Results: The nadir levels of total, myeloid, and plasmacytoid DCs occurred 8 days after infection. DC loss was partially attributable to apoptosis, which was first detected on day 5 (median parasite level, 238 parasites/mL) and maximal at day 7. Remaining DCs exhibited a reduced ability to uptake particulate antigen. DC numbers recovered approximately 60 hours after antimalarial drug administration. There was no loss of DC number or function before or after drug cure in 5 men inoculated with <180 pRBCs and treated on day 6, when their parasite level was approximately 200 parasites/mL.

     

    Conclusions: Plasmodium causes DC loss in vivo, which is at least partially explained by apoptosis in response to blood-stage parasites. In primary infection, loss of DC number and function occurs early during the prepatent period and before or with onset of clinical symptoms. These findings may explain in part the inadequate development of immunity to blood-stage malaria infection.

    Original languageEnglish
    Pages (from-to)333-340
    Number of pages8
    JournalJournal of Infectious Diseases
    Volume206
    Issue number3
    DOIs
    Publication statusPublished - 1 Aug 2012

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