Impaired in vitro Interferon-gamma production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
Author(s)
Type
Journal Article
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.
Date Issued
2022-06-24
Date Acceptance
2022-05-30
Citation
PLoS Neglected Tropical Diseases, 2022, 16 (6), pp.1-12
ISSN
1935-2727
Publisher
Public Library of Science
Start Page
1
End Page
12
Journal / Book Title
PLoS Neglected Tropical Diseases
Volume
16
Issue
6
Copyright Statement
Copyright: © 2022 Takele et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000841556000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Parasitology
Tropical Medicine
TARGET
PD-1
Publication Status
Published
Article Number
ARTN e0010544
Date Publish Online
2022-06-24