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 |
|---|---|
| Format: | Artigo |
| Language: | Inglês |
| Published: |
Frontiers
2019
|
| Subjects: | |
| Online Access: |
http://repositorio.unb.br/handle/10482/33985 https://doi.org/10.3389/fimmu.2018.01021 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: |
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. |
|---|