Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation
Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation
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DOI：
10.1002/eji.201141926
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发表时间：
2012-05-01
影响因子：
5.4
通讯作者：
Afonso, Luis C. C.
中科院分区：
文献类型：
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作者：
Figueiredo, Amanda B.;Serafim, Tiago D.;Afonso, Luis C. C.
树突状细胞（dc）在免疫反应的调节中起着至关重要的作用，一些研究已经评估了利什曼原虫和树突状细胞之间的相互作用。虽然细胞外ATP具有促炎特性，但腺苷是重要的抗炎介质。在这里，我们研究了利什曼原虫感染对DC反应的影响以及嘌呤能信号在这一过程中的参与。与未感染利什曼原虫的C57BL/6J小鼠相比，感染亚马逊利什曼原虫、巴西利什曼原虫或利什曼原虫的骨髓源树突状细胞（bmdc）的主要组织相容性复合体（MHC） II类和CD86表达降低，外核肽酶表达增加。此外，亚马逊乳杆菌感染的树突状细胞CD40表达较低，诱导t细胞增殖的能力下降。MRS1754是一种高选择性的A2B腺苷受体拮抗剂，在感染时，MRS1754的存在增加了亚马逊河乳杆菌感染的dc中MHCⅱ类、CD86和CD40的表达，并恢复了感染dc诱导t细胞增殖的能力。通过苏拉明抑制细胞外ATP水解获得了类似的结果。综上所述，我们认为亚马孙猕猴桃可能利用A2B受体激活抑制DC功能，逃避免疫应答。
Dendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex (MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A2B adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A2B receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response.