Tick saliva inhibits differentiation, maturation and function of murine bone-marrow-derived dendritic cells
Tick saliva inhibits differentiation, maturation and function of murine bone-marrow-derived dendritic cells
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DOI：
10.1111/j.1365-2567.2004.02079.x
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发表时间：
2005-02-01
期刊：
影响因子：
6.4
通讯作者：
Ferreira, BR
中科院分区：
文献类型：
--
作者：
Cavassani, KA;Aliberti, JC;Ferreira, BR
吸血性节肢动物媒介如蚊子、采采蝇、白蛉和蜱已经进化出唾液免疫调节因子，其防止脊椎动物宿主排斥它们，同时增强病原体传播。由于树突状细胞（DC）在宿主免疫应答中起重要作用，我们研究了血红扇头蜱唾液对DC分化和成熟的影响。流式细胞仪分析显示，唾液骨髓细胞抑制DC的分化，并减少了分化的未成熟DC的人口，增加主要组织相容性复合物（MHC）II类的水平，而不改变共刺激（CD 40，CD 80和CD 86）和粘附（CD 54）分子的表达。此外，成熟的DC刺激的脂多糖（LPS）在唾液的存在下，导致在较低的共刺激分子的表达，但并没有改变MHC II类和CD 54的上调。与唾液一起培养的脂多糖（LPS）成熟DC也呈现白细胞介素-12的产生减少，而白细胞介素-10的产生没有改变。用蜱唾液培养的DC的功能的评估显示它们是抗原特异性T细胞产生细胞因子的不良刺激物。我们的数据表明，在免疫反应的初始步骤，通过抑制DC分化和成熟为功能性抗原呈递细胞的节肢动物载体的唾液的一种新的调节作用。
Haematophagous arthropod vectors such as mosquitoes, tsetse flies, sandflies and ticks have evolved salivary immunomodulatory factors that prevent the vertebrate host from rejecting them meanwhile enhancing pathogen transmission. As dendritic cells (DC) play a major role in host immune responses, we studied the effects of Rhipicephalus sanguineus tick saliva on DC differentiation and maturation. Flow cytometry analysis revealed that the addition of saliva to bone marrow cells inhibits the differentiation of DC and decreased the population of differentiated immature DC, increasing the levels of major histocompatibility complex (MHC) class II while not altering the expression of costimulatory (CD40, CD80 and CD86) and adhesion (CD54) molecules. Furthermore, maturation of DC stimulated by lipopolysaccharide (LPS) in the presence of saliva resulted in a lower expression of costimulatory molecules, but did not alter the up-regulation of MHC class II and CD54. The lipopolysaccharide (LPS)-matured DC cultured with saliva also presented reduced production of interleukin-12, whereas interleukin-10 production was unaltered. Assessment of the function of DC cultured with tick saliva revealed them to be poor stimulators of cytokine production by antigen-specific T cells. Our data indicate a novel modulatory role for the saliva of arthropod vectors at an initial step of the immune response through the inhibition of differentiation and maturation of DC into functional antigen-presenting cells.