Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases
Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases
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DOI：
10.3389/fimmu.2017.01954
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发表时间：
2018-01-11
影响因子：
7.3
通讯作者：
de Almeida, Roque Pacheco
中科院分区：
文献类型：
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作者：
de Aguiar Peres, Nalu Teixeira;Seraphim Cunha, Luana Celina;de Almeida, Roque Pacheco
外核苷酸酶活性参与利什曼原虫和各种其他寄生虫的感染过程，能够调节宿主免疫应答以促进疾病进展。负责这种活性的酶之一是外三磷酸核苷二磷酸水解酶（E-NTPD酶）。该酶将核苷酸三磷酸和/或二磷酸水解成单磷酸产物，其随后水解成腺苷。这些核苷酸可以作为嘌呤能信号分子参与不同的细胞过程，管理免疫反应。鉴于这些核苷酸在细胞内病原体感染过程中细胞外代谢的重要性，本研究评估了婴儿利什曼原虫（L。infantum）感染。在L.婴儿在嘌呤饥饿、腺苷富集培养基中或在存在外核苷酸酶抑制剂的情况下。结果表明，E-NTPD酶在L.婴儿寄生虫，包括在细胞膜上。此外，根据培养基中腺苷的可用性调节酶的功能活性。嘌呤饥饿增加了核苷酸的水解能力，导致更高的感染性，而在腺苷富集培养基中生长导致感染性降低。抑制E-NTPD酶功能可降低L.巨噬细胞中的婴儿感染，表明该酶可能作为配体。综合考虑，L.婴儿水解核苷酸的能力与巨噬细胞中感染性的增加直接相关。
Ecto-nucleotidase activity is involved in the infection process of Leishmania and various other parasites that enables modulation of host immune responses to promote disease progression. One of the enzymes responsible for this activity is the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase). The enzyme hydrolyzes nucleotides tri- and/or di-phosphate into monophosphate products, which are subsequently hydrolyzed into adenosine. These nucleotides can serve as purinergic signaling molecules involved in diverse cellular processes that govern immune responses. Given the importance of the extracellular metabolism of these nucleotides during intracellular pathogen infections, this study evaluates the role of ecto-nucleotidase activity during Leishmania infantum (L. infantum) infection in human macrophages. E-NTPDase protein expression and activity was evaluated in L. infantum during purine starvation, adenosine-enriched medium, or in the presence of an inhibitor of ecto-nucleotidases. Results show that E-NTPDase is expressed in L. infantum parasites, including on the cell membrane. Furthermore, functional activity of the enzyme was modulated according to the availability of adenosine in the medium. Purine starvation increased the hydrolytic capacity of nucleotides leading to higher infectivity, while growth in adenosine-enriched medium led to lower infectivity. Moreover, inhibiting E-NTPDase function decreased L. infantum infection in macrophages, suggesting the enzyme may serve as a ligand. Taken together, the ability of L. infantum to hydrolyze nucleotides is directly associated with increased infectivity in macrophages.