Department of Bioengineering, University of Washington, Seattle, WA, USA.
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Nanomedicine. 2017 Aug;13(6):2015-2025. doi: 10.1016/j.nano.2017.04.012. Epub 2017 Apr 20.
To prime adaptive immune responses from the female reproductive tract (FRT), particulate antigens must be transported to draining lymph nodes (dLNs) since there are no local organized lymphoid structures equivalent to those found in the respiratory or gastrointestinal tracts. However, little is known about how to safely and effectively navigate successive barriers to transport such as crossing the epithelium and gaining access to migratory cells and lymphatic drainage that provide entry into dLNs. Here, we demonstrate that intravaginal pre-treatment with chitosan significantly facilitates translocation of nanoparticles (NPs) across the multilayered vaginal epithelium to target dLNs. In addition, chitosan pre-treatment was found to enhance NP associations with immunogenic antigen presenting cells in the vaginal submucosa. These observations indicate that chitosan may have great potential as an adjuvant for both local and systemic protective immunity against viral infections in the FRT.
为了从女性生殖道(FRT)引发适应性免疫反应,由于不存在与呼吸道或胃肠道等效的局部组织性淋巴结构,因此必须将颗粒状抗原运送到引流淋巴结(dLN)。然而,人们对如何安全有效地跨越连续的屏障以进行运输知之甚少,例如穿过上皮细胞并进入提供进入 dLN 的迁移细胞和淋巴引流。在这里,我们证明阴道内预先用壳聚糖处理可显著促进纳米颗粒(NP)穿过多层阴道上皮向 dLN 的转移。此外,发现壳聚糖预处理可增强 NP 与阴道黏膜下层中的免疫原性抗原呈递细胞的关联。这些观察结果表明,壳聚糖可能具有巨大的潜力,可作为局部和全身针对 FRT 中病毒感染的保护性免疫的佐剂。