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

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...

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Autores principales: Takele, Yegnasew, Adem, Emebet, Franssen, Susanne Ursula, Womersley, Rebecca, Kaforou, Myrsini, Levin, Michael, Müller, Ingrid, Cotton, James Anthony, Kropf, Pascale
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262188/
https://www.ncbi.nlm.nih.gov/pubmed/35749568
http://dx.doi.org/10.1371/journal.pntd.0010544
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author Takele, Yegnasew
Adem, Emebet
Franssen, Susanne Ursula
Womersley, Rebecca
Kaforou, Myrsini
Levin, Michael
Müller, Ingrid
Cotton, James Anthony
Kropf, Pascale
author_facet Takele, Yegnasew
Adem, Emebet
Franssen, Susanne Ursula
Womersley, Rebecca
Kaforou, Myrsini
Levin, Michael
Müller, Ingrid
Cotton, James Anthony
Kropf, Pascale
author_sort Takele, Yegnasew
collection PubMed
description 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.
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spelling pubmed-92621882022-07-08 Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation Takele, Yegnasew Adem, Emebet Franssen, Susanne Ursula Womersley, Rebecca Kaforou, Myrsini Levin, Michael Müller, Ingrid Cotton, James Anthony Kropf, Pascale PLoS Negl Trop Dis Research Article 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. Public Library of Science 2022-06-24 /pmc/articles/PMC9262188/ /pubmed/35749568 http://dx.doi.org/10.1371/journal.pntd.0010544 Text en © 2022 Takele et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Takele, Yegnasew
Adem, Emebet
Franssen, Susanne Ursula
Womersley, Rebecca
Kaforou, Myrsini
Levin, Michael
Müller, Ingrid
Cotton, James Anthony
Kropf, Pascale
Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
title Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
title_full Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
title_fullStr Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
title_full_unstemmed Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
title_short Impaired in vitro Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
title_sort impaired in vitro interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of pd1/pdl-1 ligation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262188/
https://www.ncbi.nlm.nih.gov/pubmed/35749568
http://dx.doi.org/10.1371/journal.pntd.0010544
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