Vaccination with recombinant Brugia malayi cystatin proteins alters worm migration, homing and final niche selection following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae

Vaccination with recombinant Brugia malayi cystatin proteins alters worm migration, homing and final niche selection following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae
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DOI:
10.1186/1756-3305-7-43
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发表时间:
2014-01-22
影响因子:
3.2
通讯作者:
Klei, Thomas R.
Klei, Thomas R.
中科院分区:
医学2区
文献类型:
--
作者:
Arumugam, Sridhar;Zhan, Bin;Klei, Thomas R.

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背景:马来丝虫的半胱氨酸蛋白酶抑制剂被认为参与了寄生虫的发育以及免疫调节宿主的免疫反应。在螺旋螺中,已经证明在小鼠扩散室接种模型中,Onchystatin可以诱导部分保护作用。在本研究中,我们研究了重组BM-CPI-1和BM-CPI-2蛋白接种对沙土鼠抗马来丝虫三期幼虫皮下攻击的影响。结果:用大肠杆菌衍生的重组马来伊蚊半胱氨酸蛋白酶抑制剂(BM-CPI-1或-2)接种沙土鼠不能抵抗马来丝虫L3攻击感染,但改变了相当数量的成虫从淋巴管到心脏和肺的归巢。结论:BM-CPI疫苗诱导的蠕虫迁移与我们先前观察到的巴氏杆菌排泄分泌蛋白(BM-CPI-1或-2)免疫沙土鼠的变化一致。这导致了L3的延迟迁移,并改变了成虫的最终位置。在接种犬钩吻线虫蛋白的狗身上也有类似的观察;在结肠而不是预期的小肠中发现了更多的蠕虫。另外两种肠道线虫的免疫宿主和非免疫宿主的最终生态位也发生了变化。接种疫苗导致寄生虫最终归宿的改变可能是一种罕见或常见的现象,不幸的是,这种现象很少被记录下来。成虫在接种疫苗后最终的生态位选择发生变化的原因尚不清楚,需要进一步调查。
Background: Cysteine protease inhibitors of Brugia malayi have been ascribed to be involved in parasite development as well as to immunomodulate the host's immune response. In Onchocerca volvulus, Onchocystatin has been shown to induce partial protection in the mouse diffusion chamber vaccination model. In the present study we investigated the impact of vaccination with recombinant Bm-CPI-1 and Bm-CPI-2 proteins on protection against a subcutaneous challenge of B. malayi third stage larvae in gerbils.Findings: Vaccination with E. coli derived recombinant B. malayi cysteine protease inhibitors (Bm-CPI-1 or -2) did not confer protection against B. malayi L3 challenge infection in gerbils but altered the homing of a significant number of adult worms from the lymphatics to the heart and lungs.Conclusion: Bm-CPI vaccination-induced alteration in worm migration is consistent with our previous observations in gerbils vaccinated with B. pahangi excretory-secretory (ES) proteins, which resulted in delayed migration of the L3s and altered the final location of adult worms. Similar observations have also been made in dogs vaccinated with Ancylostoma caninum proteins; an increased number of worms were recovered in the colon and not the expected small intestine. A change in the final niche was also reported in immune versus non-immune hosts of two other gut dwelling nematodes. Vaccination induced alteration of the parasite's final homing might be a rare or a common phenomenon, which unfortunately is rarely recorded. The reason for the alteration in the final niche selection by adult nematode worms following vaccination is unknown and necessitates further investigation.