Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity
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 amazonens...
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Published in | Frontiers in immunology Vol. 12; p. 598943 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
15.06.2021
|
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors share senior authorship Edited by: Fabienne Tacchini-Cottier, University of Lausanne, Switzerland This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology Reviewed by: Jaqueline França-Costa, Federal University of Bahia, Brazil; Hira Nakhasi, Center of Biologics Evaluation and Research (FDA), United States |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2021.598943 |