Título:	PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis
Autor(es):	Barroso, Daniel Holanda Falcão, Sarah de Athayde Couto Motta, Jorgeth de Oliveira Carneiro da Santos, Laís Sevilha dos Takano, Gustavo Henrique Soares Gomes, Ciro Martins Favali, Cecília Beatriz Fiuza Lima, Beatriz Dolabela de Sampaio, Raimunda Nonata Ribeiro
Assunto:	Leishmaniose tegumentar Leishmania (Leishmania) amazonensis Células Enzimas Citometria
Data de publicação:	11-Mai-2018
Editora:	Frontiers
Referência:	BARROSO, Daniel Holanda et al. PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis. Frontiers in Immunology, v. 9, article 1021, May 2018. DOI: https://doi.org/10.3389/fimmu.2018.01021. Disponível em: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01021/full. Acesso em: 12 fev. 2019.
Abstract:	Introduction: Diffuse cutaneous leishmaniasis (DCL) is a rare disease form associated with Leishmania (L.) amazonensis in South America. It represents the “anergic” pole of American Tegumentary Leishmaniasis, and the explanation for its resistance to treatment remains elusive. We aimed to study some possible immunological mechanisms involved in the poor DCL treatment response by evaluating some cell surface molecules obtained from a patient with DCL by flow cytometry. Case presentation: A 65-year-old DCL patient who initially failed to respond to the standard treatment for the disease showed vacuolated macrophages filled with amastigotes in lesion biopsy, and L. (L.) amazonensis was identified through ITS1PCR amplification. The Leishmania skin test and indirect immunofluorescence analysis revealed negative results. Peripheral blood from the patient was collected after a few months of treatment, when the patient presented with no lesion. Peripheral blood mononuclear cells were analyzed ex vivo and in vitro after 48 h of stimulation with soluble L. (L.) amazonensis antigen (SLA). Cell death, surface molecules, and intracellular molecules, such as IFN-γ and granzyme B, were analyzed in the cells using flow cytometry. Analysis of the surface markers showed an increased expression of the inhibitory molecule programmed death ligand 1 (PD-L1) in the monocytes restimulated with SLA (approximately 65%), whereas the negative controls were 35% positive for PD-L1. Conversely, compared with the negative controls, we observed a decrease in CD4+IFN-γ+ T cells (8.32 versus 1.7%) and CD8+IFN-γ+ T cells (14% versus 1%). We also observed a relevant decrease in the granzyme B levels in the CD8+ T cells, from 31% in the negative controls to 5% after SLA restimulation. Conclusion: The dysfunctional activation of PD-L1 inhibitory pathway after Leishmania antigen stimulation and reduced levels of IFN-gamma and granzyme B-producing cells could be closely related to unresponssiveness to standard drug treatment of DCL patient.
Unidade Acadêmica:	Faculdade de Medicina (FMD)
Licença:	Copyright © 2018 Barroso, Falcão, Motta, Sevilha-Santos, Takano, Gomes, Favali, de Lima and Sampaio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI:	https://doi.org/10.3389/fimmu.2018.01021
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