Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity.
Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity.
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DOI：
10.3389/fimmu.2021.598943
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发表时间：
2021
影响因子：
7.3
通讯作者：
de Matos Guedes HL
中科院分区：
文献类型：
--
作者：
da Fonseca-Martins AM;de Souza Lima-Gomes P;Antunes MM;de Moura RG;Covre LP;Calôba C;Rocha VG;Pereira RM;Menezes GB;Gomes DCO;Saraiva EM;de Matos Guedes HL
中性粒细胞在利什曼病的转归中起重要作用，有助于加重或控制感染的进展，这是一种双重作用，其潜在机制尚不清楚。我们最近报道了亚马逊利什曼原虫感染小鼠的CD 4+和CD 8 + T细胞以及树突状细胞分别高表达PD-1和PD-L1。鉴于PD-1/PD-L1相互作用可能促进细胞功能障碍，并且中性粒细胞在感染期间可能与T细胞相互作用，我们在此研究了暴露于利什曼原虫寄生虫的中性粒细胞中的PD-L1水平。我们发现，L. amazonensis诱导PD-L1在体外内化这些寄生虫的人和鼠嗜中性粒细胞中的表达。在耳病变和L的引流淋巴结中也观察到PD-L1表达中性粒细胞。亚马逊河病毒感染的小鼠，通过细胞计数和活体显微镜进行评估。此外，随着疾病进展到慢性期，来自耳部病变的中性粒细胞中PD-L1的表达逐渐增加。感染的中性粒细胞与体外活化的CD 8 + T细胞共培养通过依赖于PD-1和PD-L1的机制抑制IFN-γ的产生。重要的是，我们证明了巴西乳杆菌体外感染人中性粒细胞诱导PD-L1+表达，并且在皮肤利什曼病患者的病变中检测到PD-L1+中性粒细胞。总之，这些发现表明利什曼原虫增加了具有抑制能力的中性粒细胞中PD-L1的表达，这可能通过损害免疫反应而有利于寄生虫的存活。
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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影响因子：
7.3
作者：
Garcia de Moura R;Covre LP;Fantecelle CH;Gajardo VAT;Cunha CB;Stringari LL;Belew AT;Daniel CB;Zeidler SVV;Tadokoro CE;de Matos Guedes HL;Zanotti RL;Mosser D;Falqueto A;Akbar AN;Gomes DCO
通讯作者：
Gomes DCO
影响因子：
3.1
作者：
Carlsen, Eric D.;Hay, Christie;Soong, Lynn
通讯作者：
Soong, Lynn
影响因子：
7.3
作者：
Barroso, Daniel Holanda;Couto Falcao, Sarah De Athayde;Ribeiro Sampaio, Raimunda Nonata
通讯作者：
Ribeiro Sampaio, Raimunda Nonata
影响因子：
2.6
作者：
Araujo Vercosa, Barbara Laurice;Melo, Maria Norma;Vasconcelos, Anilton Cesar
通讯作者：
Vasconcelos, Anilton Cesar
影响因子：
2.8
作者：
Chiku, Vanessa Marim;Oliveira Silva, Kathlenn Liezbeth;Felix de Lima, Valeria Marcal
通讯作者：
Felix de Lima, Valeria Marcal