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首页> 外文期刊>Infection and immunity >Dual Role of the Leishmania majorRibosomal Protein S3a Homologue in Regulation of T- and B-Cell Activation
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Dual Role of the Leishmania majorRibosomal Protein S3a Homologue in Regulation of T- and B-Cell Activation

机译：利什曼原虫主要核糖体蛋白S3a同源物在调节T细胞和B细胞活化中的双重作用

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We have recently characterized a novel Leishmania majorgene encoding a polypeptide of 30 kDa that was homologous to mammalian ribosomal protein S3a and was named LmS3a-related protein (LmS3arp). The protein was found to be expressed by all the Leishmaniaspecies so far examined (L. infantum, L. amazonensis, andL. mexicana). In the present study we have extended our approach to the analysis of LmS3arp activity on T- and B-cell functions in a murine model. The results presented in this report show that LmS3arp plays a dual role in the regulation of T- and B-cell reactivity. Indeed, we found that injection of the LmS3arp recombinant protein (rLmS3arp) into BALB/c mice induces preferential activation of B cells, as shown by the following criteria: (i) increased expression of CD69 molecules on immunoglobulin M (IgM)-secreting spleen cells, (ii) a considerable increase of IgM-secreting B cells, and (iii) elevated levels of IgM antibodies in the sera of injected animals. Moreover, the IgM antibodies are not specific to theLeishmania antigens but preferentially recognize heterologous antigens like myosin, thyroglobulin, DNA, and keyhole limpet hemocyanin. Furthermore, the strong polyclonal expansion of nonspecific, non-parasite-directed B-cell clones induced by rLmS3arp is concomitant with a marked inhibition of T-cell proliferation. Analysis of cytokine production revealed a significant downregulation of gamma interferon, interleukin-2 (IL-2), and IL-12 secretion. Taken together, our data suggest that rLmS3arp, through direct or indirect action toward B and T cells and cytokine secretion, could participate in the immunoregulatory processes that play a role in the balance of the Th1 and Th2 immune response.
机译：最近，我们表征了一个新的 Leishmania major 基因，该基因编码与哺乳动物核糖体蛋白S3a同源的30 kDa多肽，被称为LmS3a相关蛋白（LmS3arp）。迄今为止，发现该蛋白在所有利什曼原虫物种中均有表达（婴儿乳杆菌，亚马逊乳杆菌和墨西哥乳杆菌）。 。在本研究中，我们已经将我们的方法扩展到了鼠模型中LmS3arp对T细胞和B细胞功能的活性分析。本报告中的结果表明，LmS3arp在调节T细胞和B细胞反应性中起着双重作用。实际上，我们发现将LmS3arp重组蛋白（rLmS3arp）注射到BALB / c小鼠中会诱导B细胞优先激活，如以下标准所示：（i）分泌免疫球蛋白M（IgM）的脾脏中CD69分子的表达增加细胞;（ii）分泌IgM的B细胞大量增加，以及（iii）注射动物血清中的IgM抗体水平升高。此外，IgM抗体并非对利什曼原虫抗原具有特异性，但会优先识别异源抗原，如肌球蛋白，甲状腺球蛋白，DNA和匙孔血蓝蛋白。此外，rLmS3arp诱导的非特异性，非寄生虫定向的B细胞克隆的强大多克隆扩增伴随着对T细胞增殖的明显抑制。细胞因子产生的分析显示，γ干扰素，白介素2（IL-2）和IL-12分泌显着下调。两者合计，我们的数据表明，rLmS3arp通过直接或间接作用于B细胞和T细胞以及细胞因子的分泌，可以参与免疫调节过程，从而在Th1和Th2免疫应答的平衡中发挥作用。

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