Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation

Takele, Y., Adem, E., Ursula Franssen, S., Womersley, R., Kaforou, M., Levin, M., Müller, I., Cotton, J. A. and Kropf, P. (2022) Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation. PLoS Neglected Tropical Diseases, 16(6), e0010544. (doi: 10.1371/journal.pntd.0010544) (PMID:35749568) (PMCID:PMC9262188)

Abstract

Visceral leishmaniasis (VL) is a neglected tropical disease that causes substantial morbidity and mortality and is a growing health problem in Ethiopia, where this study took place. Most individuals infected with Leishmania donovani parasites will stay asymptomatic, but some develop VL that, if left untreated, is almost always fatal. This stage of the disease is associated with a profound immunosuppression, characterised by impaired production of Interferonγ (IFNγ), a cytokine that plays a key role in the control of Leishmania parasites, and high expression levels of an inhibitory receptor, programmed cell death 1 (PD1) on CD4+ T cells. Here, we tested the contribution of the interaction between the immune checkpoint PD1 and its ligand PDL-1 on the impaired production of IFNγ in VL patients. Our results show that in the blood of VL patients, not only CD4+, but also CD8+ T cells express high levels of PD1 at the time of VL diagnosis. Next, we identified PDL-1 expression on different monocyte subsets and neutrophils and show that PDL-1 levels were significantly increased in VL patients. PD1/PDL-1 inhibition resulted in significantly increased production of IFNγ, suggesting that therapy using immune checkpoint inhibitors might improve disease control in these patients.

• Item Type: Articles
• Additional Information: Funding: YT is funded by a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine (204797/Z/16/Z). JAC is funded by Wellcome via core funding of the Wellcome Sanger Institute (grant 206194). MK is funded by a Wellcome Trust Sir Henry Wellcome Fellowship (206508/Z/17/Z).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cotton, Professor James

Creator Roles

Cotton, J.: Formal analysis, Writing – original draft, Writing – review and editing

• Authors: Takele, Y., Adem, E., Ursula Franssen, S., Womersley, R., Kaforou, M., Levin, M., Müller, I., Cotton, J. A., and Kropf, P.
• College/School: College of Arts & Humanities > School of Humanities > Information Studies
• Journal Name: PLoS Neglected Tropical Diseases
• Publisher: Public Library of Science
• ISSN: 1935-2727
• ISSN (Online): 1935-2735
• Published Online: 24 June 2022
• Copyright Holders: Copyright: © 2022 Takele et al
• First Published: First published in PLoS Neglected Tropical Diseases 16(6): e0010544
• Publisher Policy: Reproduced under a Creative Commons License