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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Modulation of dendritic cell function and immune response by cysteine protease inhibitor from murine nematode parasite Heligmosomoides polygyrus
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Modulation of dendritic cell function and immune response by cysteine protease inhibitor from murine nematode parasite Heligmosomoides polygyrus

机译：半胱氨酸蛋白酶抑制剂对小鼠线虫寄生性多毛回旋虫半胱氨酸蛋白酶抑制剂的树突状细胞功能和免疫应答的调节

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Summary: Modulation and suppression of the immune response of the host by nematode parasites have been reported extensively and the cysteine protease inhibitor (CPI or cystatin) is identified as one of the major immunomodulators. In the present study, we cloned and produced recombinant CPI protein from the murine nematode parasite Heligmosomoides polygyrus (rHp-CPI) and investigated its immunomodulatory effects on dendritic cell (DC) function and immune responses in mice. Bone-marrow-derived CD11c+ DC (BMDC) that were exposed to rHp-CPI during the differentiation stage showed reduced MHC-II molecule expression compared with BMDC that were generated in normal culture conditions. The BMDC generated in the presence of rHp-CPI also exhibited reduced expression of CD40, CD86 and MHC-II molecules and reduced interleukin-6 and tumour necrosis factor-α cytokine production when stimulated with Toll-like receptor ligand CpG. Activation of BMDC generated in normal conditions induced by lipopolysaccharide and CpG was also suppressed by rHp-CPI, as shown by reduced co-stimulatory molecule expression and cytokine production. Furthermore, BMDC treated with rHp-CPI before ovalbumin (OVA) antigen pulsing induced a weaker proliferation response and less interferon-γ production of OVA-specific CD4+ T cells compared with BMDC without rHp-CPI pre-treatment. Adoptive transfer of rHp-CPI-treated and OVA-loaded BMDC to mice induced significantly lower levels of antigen-specific antibody response than the BMDC loaded with antigen alone. These results demonstrated that the CPI from nematode parasites is able to modulate differentiation and activation stages of BMDC. It also interferes with antigen and MHC-II molecule processing and Toll-like receptor signalling pathway, resulting in functionally deficient DC that induce a suboptimum immune response.
机译：摘要：线虫寄生虫对宿主免疫应答的调节和抑制已得到广泛报道，并且半胱氨酸蛋白酶抑制剂（CPI或cystatin）被确定为主要的免疫调节剂之一。在本研究中，我们从鼠线虫寄生性多毛回旋线虫（rHp-CPI）克隆并生产了重组CPI蛋白，并研究了其对小鼠树突状细胞（DC）功能和免疫应答的免疫调节作用。与正常培养条件下产生的BMDC相比，在分化阶段暴露于rHp-CPI的骨髓来源的CD11c + DC（BMDC）显示出降低的MHC-II分子表达。当用Toll样受体配体CpG刺激时，在存在rHp-CPI的情况下生成的BMDC还表现出CD40，CD86和MHC-II分子表达降低，白介素6和肿瘤坏死因子-α细胞因子生成降低。 rHp-CPI也抑制了由脂多糖和CpG诱导的正常条件下产生的BMDC的激活，如共刺激分子表达和细胞因子生成的降低。此外，与未经rHp-CPI预处理的BMDC相比，在卵清蛋白（OVA）抗原脉冲作用之前用rHp-CPI处理的BMDC诱导了较弱的增殖反应并且OVA特异性CD4 + T细胞的干扰素-γ产生较少。经过rHp-CPI处理和OVA加载的BMDC的过继转移比单独加载抗原的BMDC显着降低了抗原特异性抗体反应的水平。这些结果表明线虫寄生虫的CPI能够调节BMDC的分化和激活阶段。它还会干扰抗原和MHC-II分子的加工以及Toll样受体的信号传导途径，导致功能不足的DC诱导亚最佳免疫反应。

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