PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis
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 s...
| Main Authors: | 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 |
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ir-10482-339852019-02-12T11:23:03Z PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis 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 Leishmaniose tegumentar Leishmania (Leishmania) amazonensis Células Enzimas Citometria 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. 2019-02-12T11:20:59Z 2019-02-12T11:20:59Z 2018-05-11 Artigo 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. http://repositorio.unb.br/handle/10482/33985 https://doi.org/10.3389/fimmu.2018.01021 Inglês Acesso Aberto 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. application/pdf Frontiers |
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| language |
Inglês |
| topic |
Leishmaniose tegumentar Leishmania (Leishmania) amazonensis Células Enzimas Citometria |
| spellingShingle |
Leishmaniose tegumentar Leishmania (Leishmania) amazonensis Células Enzimas Citometria 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 PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis |
| description |
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. |
| format |
Artigo |
| author |
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 |
| author_sort |
Barroso, Daniel Holanda |
| title |
PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis |
| title_short |
PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis |
| title_full |
PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis |
| title_fullStr |
PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis |
| title_full_unstemmed |
PD-L1 may mediate T-cell exhaustion in a case of early diffuse Leishmaniasis caused by Leishmania (L.) amazonensis |
| title_sort |
pd-l1 may mediate t-cell exhaustion in a case of early diffuse leishmaniasis caused by leishmania (l.) amazonensis |
| publisher |
Frontiers |
| publishDate |
2019 |
| url |
http://repositorio.unb.br/handle/10482/33985 https://doi.org/10.3389/fimmu.2018.01021 |
| _version_ |
1641988458359554048 |
| score |
13.657419 |