Macrophage migration inhibitory factor homolog from Plasmodium yoelii modulates monocyte recruitment and activation in spleen during infection.

Macrophage migration inhibitory factor homolog from Plasmodium yoelii modulates monocyte recruitment and activation in spleen during infection.
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DOI:
10.1007/s00436-011-2696-6
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发表时间:
2012-05
影响因子:
2
通讯作者:
Long C
Long C
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Y;Miura K;Li J;Tullo G;Zhu F;Hong L;Lin T;Su XZ;Long C

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巨噬细胞移动抑制因子(MIF)已被证明参与严重疟疾的发病机制。疟疾寄生虫表达可能在调节宿主免疫应答中起作用的MIF同源物,并且最近的研究表明MIF的过表达减少了小鼠疟疾模型中的寄生虫血症。最近的另一项研究表明,单核细胞迁移到脾脏有助于控制血液阶段感染。然而,很少有文章描述MIF对感染过程中单核细胞募集/活化的影响。我们制备了重组约氏疟原虫MIF(rPyMIF),并研究了其对体外纯化的小鼠CD 11b+细胞和体内单核细胞反应的作用。结果表明,rPyMIF蛋白能与小鼠CD 11b+细胞结合,并能抑制CD 11b+细胞的随机迁移。另一方面,rPyMIF不直接诱导细胞释放细胞因子或调节LPS诱导的细胞因子释放。用rPyMIF免疫的小鼠在致死性Py 17 XL攻击后第3天表现出短暂的但显著低于对照小鼠的寄生虫血症。rPyMIF免疫组脾脏中CD 11b+细胞总数显著高于对照组。进一步研究发现,rPyMIF免疫组在第3天脾脏中有显著更高数量的募集和活化的单核细胞。这些结果表明,PyMIF在感染约氏疟原虫红细胞阶段期间潜在地调节单核细胞募集和活化。
Macrophage migration inhibitory factor (MIF) has been shown to be involved in the pathogenesis of severe malaria. Malaria parasites express an MIF homolog that may play a role in regulating host immune responses and a recent study showed that overexpression of MIF reduced parasitemia in a mouse malaria model. Another recent study showed migration of monocytes to the spleen contributed to the control of blood stage infection. However, there are few papers describing the effect of MIF on monocyte recruitment/activation during the infection. We generated recombinant P. yoelii MIF (rPyMIF) and investigated its function on purified mouse CD11b+ cells in vitro and monocyte responses in vivo. The result shows that rPyMIF protein bound to mouse CD11b+ cells and inhibited their random migration in vitro. On the other hand, rPyMIF did not induce cytokine release from the cells directly or modulate LPS-induced cytokine release. Mice immunized with rPyMIF showed transient, but significantly lower parasitemia than the control mice at day 3 after lethal Py17XL challenge. The total number of CD11b+ cells in the spleens was significantly higher in rPyMIF-immunized group. Further investigation revealed that there were significantly higher numbers of recruited and activated monocytes in the spleens of rPyMIF immunization group on day 3. These results indicate that PyMIF potentially modulates monocyte recruitment and activation during infection of P. yoelii erythrocytic stages.
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