Imperial College London
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ProfessorMichaelLevin

Faculty of Medicine, Department of Infectious Disease

Chair in Paediatrics & International Child Health
 
 
 
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Contact

 

+44 (0)20 7594 3760m.levin Website

 
 
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Location

 

233Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Takele:2021:10.1101/2021.11.01.466750,
author = {Takele, Y and Adem, E and Franssen, SU and Womersley, R and Kaforou, M and Levin, M and Müller, I and Cotton, JA and Kropf, P},
doi = {10.1101/2021.11.01.466750},
title = {Impaired <i>in vitro</i> Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation},
url = {http://dx.doi.org/10.1101/2021.11.01.466750},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>ABSTRACT</jats:title><jats:p>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 <jats:italic>Leishmania donovani</jats:italic> 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 <jats:italic>Leishmania</jats:italic> parasites, and high expression levels of an inhibitory receptor, programmed cell death 1 (PD1) on CD4<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup>, but also CD8<jats:sup>+</jats:sup> 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.</jats:p>
AU  - Takele,Y
AU  - Adem,E
AU  - Franssen,SU
AU  - Womersley,R
AU  - Kaforou,M
AU  - Levin,M
AU  - Müller,I
AU  - Cotton,JA
AU  - Kropf,P
DO  - 10.1101/2021.11.01.466750
PY  - 2021///
TI  - Impaired <i>in vitro</i> Interferon-γ production in patients with visceral leishmaniasis is improved by inhibition of PD1/PDL-1 ligation
UR  - http://dx.doi.org/10.1101/2021.11.01.466750
ER  -
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