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Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity

da Fonseca-Martins, AM; de Souza Lima-Gomes, P; Antunes, MM; de Moura, RG; Covre, LP; Calôba, C; Rocha, VG; ... de Matos Guedes, HL; + view all (2021) Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity. Frontiers in Immunology , 12 10.3389/fimmu.2021.598943. Green open access

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Abstract

Neutrophils play an important role in the outcome of leishmaniasis, contributing either to exacerbating or controlling the progression of infection, a dual effect whose underlying mechanisms are not clear. We recently reported that CD4+ and CD8+ T cells, and dendritic cells of Leishmania amazonensis-infected mice present high expression of PD-1 and PD-L1, respectively. Given that the PD-1/PD-L1 interaction may promote cellular dysfunction, and that neutrophils could interact with T cells during infection, we investigated here the levels of PD-L1 in neutrophils exposed to Leishmania parasites. We found that both, promastigotes and amastigotes of L. amazonensis induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites in vitro. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of L. amazonensis-infected mice, assessed through cell cytometry and intravital microscopy. Moreover, expression of PD-L1 progressively increased in neutrophils from ear lesions as the disease evolved to the chronic phase. Co-culture of infected neutrophils with in vitro activated CD8+ T cells inhibits IFN-γ production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that in vitro infection of human neutrophils by L braziliensis induced PD-L1+ expression and also PD-L1+ neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the Leishmania parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response.

Type: Article
Title: Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2021.598943
Publisher version: https://doi.org/10.3389/fimmu.2021.598943
Language: English
Additional information: © 2021 da Fonseca-Martins, de Souza Lima-Gomes, Antunes, de Moura, Covre, Calôba, Rocha, Pereira, Menezes, Gomes, Saraiva and de Matos Guedes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10131311
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