Article
Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity
Registro en:
MARTINS, Alessandra M. da Fonseca et al. Leishmania parasites drive PD-L1 expression in mice and human neutrophils with suppressor capacity. Frontiers in Immunology, v. 12, Article 598943, 15 p, June 2021.
1664-3224
10.3389/fimmu.2021.598943
Autor
Martins, Alessandra M. da Fonseca
Gomes, Phillipe de Souza Lima
Antunes, Maísa Mota
Moura, Renan Garcia de
Covre, Luciana P.
Calôba, Carolina
Rocha, Vivian Grizente
Pereira, Renata M.
Menezes, Gustavo Batista
Gomes, Daniel Claudio Oliveira
Saraiva, Elvira M.
Guedes, Herbet L. de Matos
Resumen
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.