Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function
Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function
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DOI：
10.1073/pnas.2002880117
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发表时间：
2020-07-28
影响因子：
11.1
通讯作者：
Mitragotri, Samir
中科院分区：
文献类型：
--
作者：
Ukidve, Anvay;Zhao, Zongmin;Mitragotri, Samir
红细胞在循环中自然捕获某些细菌病原体，通过氧化应激杀死它们，并将它们呈递给脾中的抗原提呈细胞(APC)。通过利用红细胞的这种固有免疫功能，我们开发了红细胞驱动的免疫靶向(EDIT)，它将纳米颗粒从红细胞表面呈现到脾中的APC。抗原性纳米颗粒吸附在红细胞表面。通过引入吸附纳米颗粒的数密度(即每个红细胞负载的纳米颗粒的数量)，它们主要被输送到脾而不是肺，后者通常是红细胞介导的递送系统的靶点。与对照组相比，将红细胞递送的纳米颗粒呈现给脾可以提高对抗原的抗体反应，提高中枢记忆T细胞反应，降低调节性T细胞反应。在预防模型中，增强的免疫反应减缓了肿瘤的进展。这些发现表明，EDIT是增强系统免疫力的有效策略。
Erythrocytes naturally capture certain bacterial pathogens in cir-culation, kill them through oxidative stress, and present them to the antigen-presenting cells (APCs) in the spleen. By leveraging this innate immune function of erythrocytes, we developed erythrocyte-driven immune targeting (EDIT), which presents nanoparticles from the surface of erythrocytes to the APCs in the spleen. Antigenic nanoparticles were adsorbed on the erythrocyte surface. By engi-neering the number density of adsorbed nanoparticles, (i.e., the number of nanoparticles loaded per erythrocyte), they were pre-dominantly delivered to the spleen rather than lungs, which is con-ventionally the target of erythrocyte-mediated delivery systems. Presentation of erythrocyte-delivered nanoparticles to the spleen led to improved antibody response against the antigen, higher cen-tral memory T cell response, and lower regulatory T cell response, compared with controls. Enhanced immune response slowed down tumor progression in a prophylaxis model. These findings suggest that EDIT is an effective strategy to enhance systemic immunity.