Early changes in CD4+ T cell activation following blood-stage Plasmodium falciparum infection

Early changes in CD4+ T cell activation following blood-stage Plasmodium falciparum infection Abstract We examined transcriptional changes in CD4+ T cells during blood-stage Plasmodium falciparum infection in individuals without a history of previous parasite exposure. CD4+ T cell CXCL8 gene (encoding IL-8) transcription was identified as an early biomarker of sub-microscopic P. falciparum infection, with predictive power for parasite growth. Following anti-parasitic drug treatment, a CD4+ T cell regulatory phenotype developed. PD1 expression on CD49b+ CD4+ T (putative type I regulatory (Tr1)) cells after drug treatment negatively correlated with earlier parasite growth. Blockade of PD1 but no other immune checkpoint molecules tested, increased IFNγ and IL-10 production in an ex vivo antigen-specific cellular assay at peak of infection. These results demonstrate the early development of an immunoregulatory CD4+ T cell phenotype in blood-stage P. falciparum infection, and show selective immune check point blockade may be used to modulate early developing anti-parasitic immunoregulatory pathways as part of malaria vaccine and/or drug treatment protocols. malaria, CD4+ T cells, Plasmodium falciparum, immunoregulation © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Infectious Diseases Oxford University Press

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
ISSN
0022-1899
eISSN
1537-6613
D.O.I.
10.1093/infdis/jiy281
Publisher site
See Article on Publisher Site

Abstract

Abstract We examined transcriptional changes in CD4+ T cells during blood-stage Plasmodium falciparum infection in individuals without a history of previous parasite exposure. CD4+ T cell CXCL8 gene (encoding IL-8) transcription was identified as an early biomarker of sub-microscopic P. falciparum infection, with predictive power for parasite growth. Following anti-parasitic drug treatment, a CD4+ T cell regulatory phenotype developed. PD1 expression on CD49b+ CD4+ T (putative type I regulatory (Tr1)) cells after drug treatment negatively correlated with earlier parasite growth. Blockade of PD1 but no other immune checkpoint molecules tested, increased IFNγ and IL-10 production in an ex vivo antigen-specific cellular assay at peak of infection. These results demonstrate the early development of an immunoregulatory CD4+ T cell phenotype in blood-stage P. falciparum infection, and show selective immune check point blockade may be used to modulate early developing anti-parasitic immunoregulatory pathways as part of malaria vaccine and/or drug treatment protocols. malaria, CD4+ T cells, Plasmodium falciparum, immunoregulation © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

The Journal of Infectious DiseasesOxford University Press

Published: May 11, 2018

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