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LEISHMANIA PARASITES DRIVE PD-L1 EXPRESSION IN MICE AND HUMAN NEUTROPHILS WITH SUPPRESSOR CAPACITY
Neutrófilos
Leishmania
Pele
Leishmaniose cutânea humana
Leishmaniose murina
Hibridização Subtrativa por Supressão
Neutrophils
Skin
Leishmania
Human cutaneous leishmaniasis
Murine leishmaniasis
Supression
Author
Affilliation
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-g 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.
Keywords in Portuguese
PD-L1Neutrófilos
Leishmania
Pele
Leishmaniose cutânea humana
Leishmaniose murina
Hibridização Subtrativa por Supressão
Keywords
PD-L1Neutrophils
Skin
Leishmania
Human cutaneous leishmaniasis
Murine leishmaniasis
Supression
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