BluePort: a platform to study the eosinophilic response of mice to the bite of a vector of Leishmania parasites, Lutzomyia longipalpis sand flies.

BluePort: a platform to study the eosinophilic response of mice to the bite of a vector of Leishmania parasites, Lutzomyia longipalpis sand flies.
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DOI:
10.1371/journal.pone.0013546
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发表时间:
2010-10-27
期刊:
影响因子:
3.7
通讯作者:
Titus RG
Titus RG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mejia JS;Toot-Zimmer AL;Schultheiss PC;Beaty BJ;Titus RG

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内脏利什曼病是一种严重的人类疾病,在新大陆,由Lutzomyia longipalpis白蛉传播。流行区居民对利什曼原虫传播的天然抵抗力归因于对白蛉唾液蛋白的免疫力。加速获得这种免疫力的一种理论方法是增加白蛉叮咬部位抗原呈递细胞的密度。在这里,我们描述了一种可用于此目的的新型组织平台。BluePort是通过注射覆盖有Cibacron蓝的琼脂糖珠在小鼠皮下组织中诱导的血管化良好且富含巨噬细胞的隔室。我们描述了导致其形成的炎症事件的顺序,以及如何将其用于研究皮肤对L.长须沙蝇结果表明,炎症反应从嗜酸性粒细胞向嗜酸性粒细胞的转变是与通过反复暴露于白蛉叮咬获得的免疫相关的主要组织病理学特征,并且BluePort组织隔室可用于加速该过程。此外,在BluePort薄壁组织内观察到的变化表明,它可用于研究复杂的免疫生物学过程,并开发异位次级淋巴结构。了解白蛉叮咬后皮肤反应的特征是使用靶向唾液蛋白疫苗控制利什曼病策略的关键要素。发现皮肤嗜酸性粒细胞增多症是由反复暴露于白蛉叮咬诱导的抗唾液免疫的重要组成部分,这提出了一个重要的考虑:如何避免来自针对白蛉唾液的保护性Th2驱动免疫与针对寄生虫的保护性Th1驱动免疫的免疫冲突。BluePort平台是解决这个难题的理想工具。
Visceral Leishmaniasis is a serious human disease transmitted, in the New World, by Lutzomyia longipalpis sand flies. Natural resistance to Leishmania transmission in residents of endemic areas has been attributed to the acquisition of immunity to sand fly salivary proteins. One theoretical way to accelerate the acquisition of this immunity is to increase the density of antigen-presenting cells at the sand fly bite site. Here we describe a novel tissue platform that can be used for this purpose. BluePort is a well-vascularized and macrophage-rich compartment induced in the subcutaneous tissue of mice via injection of agarose beads covered with Cibacron blue. We describe the sequence of inflammatory events leading to its formation and how it can be used to study the dermal response to the bite of L. longipalpis sand flies. Results presented indicate that a shift in the inflammatory response, from neutrophilic to eosinophilic, is the main histopathological feature associated with the immunity acquired through repeated exposure to the bite of sand flies, and that the BluePort tissue compartment could be used to accelerate this process. In addition, changes observed inside the BluePort parenchyma indicate that it could be used to study complex immunobiological processes, and to develop ectopic secondary lymphoid structures. Understanding the characteristics of the dermal response to the bite of sand flies is a critical element of strategies to control leishmaniasis using vaccines that target salivary proteins. Finding that dermal eosinophilia is such a prominent component of the anti-salivary immunity induced by repeated exposure to sand fly bites raises one important consideration: how to avoid the immunological conflict derived from a protective Th2-driven immunity directed to sand fly saliva with a protective Th1-driven immunity directed to the parasite. The BluePort platform is an ideal tool to address experimentally this conundrum.
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期刊: The Journal of experimental medicine
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发表时间: 2010-04-01
影响因子: 4.4
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