{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:22:57Z","timestamp":1790709777476,"version":"4.1.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells, and dendritic cells of <jats:italic>Leishmania amazonensis-<\/jats:italic>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 <jats:italic>Leishmania<\/jats:italic> parasites. We found that both, promastigotes and amastigotes of <jats:italic>L. amazonensis<\/jats:italic> induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites <jats:italic>in vitro<\/jats:italic>. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of <jats:italic>L. amazonensis<\/jats:italic>-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 <jats:italic>in vitro<\/jats:italic> activated CD8<jats:sup>+<\/jats:sup> T cells inhibits IFN-\u03b3 production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that <jats:italic>in vitro<\/jats:italic> infection of human neutrophils by <jats:italic>L braziliensis<\/jats:italic> induced PD-L1<jats:sup>+<\/jats:sup> expression and also PD-L1<jats:sup>+<\/jats:sup> neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the <jats:italic>Leishmania<\/jats:italic> parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response.<\/jats:p>","DOI":"10.3389\/fimmu.2021.598943","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T14:42:03Z","timestamp":1623768123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity"],"prefix":"10.3389","volume":"12","author":[{"given":"Alessandra M.","family":"da Fonseca-Martins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipe","family":"de Souza Lima-Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u00edsa 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