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

The Journal of Infectious Diseases
Chelsea L EdwardsC R Engwerda

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 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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Citations

Feb 24, 2019·The Journal of Infectious Diseases·Shashi Bhushan ChauhanChristian Engwerda
Sep 9, 2019·Parasite Immunology·Bhawana SinghChristian Engwerda
Oct 15, 2019·Immunological Reviews·Claire LoiseauDenise L Doolan
Nov 12, 2019·Immunological Reviews·Michael F Good, Danielle I Stanisic
Nov 22, 2018·Frontiers in Immunology·Chelsea L EdwardsChristian R Engwerda
Nov 2, 2019·Immunological Reviews·Rajiv KumarChristian R Engwerda
Feb 9, 2019·Expert Review of Vaccines·Martha M CooperDenise L Doolan
Dec 8, 2020·Clinical & Translational Immunology·Simon H ApteDenise L Doolan

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