Mura Marie, Atre Tanmaya, Savransky Tatyana, Bergmann-Leitner Elke S
Immunology Core, Biologics Research & Development, WRAIR-Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Immunopathology, Microbiology and Infectious Diseases, IRBA-Institut de Recherche Biomédicale des Armées, 91220 Brétigny-sur-Orge, France.
Vaccines (Basel). 2022 Oct 21;10(10):1768. doi: 10.3390/vaccines10101768.
The onset of an adaptive immune response provides the signals required for differentiation of antigen-specific lymphocytes into effector cells and imprinting of these cells for re-circulation to the most appropriate anatomical site (i.e., homing). Lymphocyte homing is governed by the expression of tissue-specific lymphocyte homing receptors that bind to unique tissue-specific ligands on endothelial cells. In this study, a whole-parasite malaria vaccine (radiation-attenuated sporozoites (RAS)) was used as a model system to establish homing receptor signatures induced by the parasite delivered through mosquito bite to provide a benchmark of desirable homing receptors for malaria vaccine developers. This immunization regimen resulted in the priming of antigen-specific B cells and CD8 T cells for homing primarily to the skin and T/B cell compartments of secondary lymphoid organs. Infection with live sporozoites, however, triggers the upregulation of homing receptor for the liver and the skin, demonstrating that there is a difference in the signal provided by attenuated vs. live sporozoites. This is the first report on imprinting of homing routes by sporozoites and, surprisingly, it also points to additional, yet to be identified, signals provided by live parasites that prime lymphocytes for homing to the liver. The data also demonstrate the utility of this method for assessing the potential of vaccine formulations to direct antigen-specific lymphocytes to the most relevant anatomical site, thus potentially impacting vaccine efficacy.
适应性免疫反应的启动提供了抗原特异性淋巴细胞分化为效应细胞所需的信号，并为这些细胞重新循环至最合适的解剖部位（即归巢）进行印记。淋巴细胞归巢由组织特异性淋巴细胞归巢受体的表达所调控，这些受体与内皮细胞上独特的组织特异性配体结合。在本研究中，一种全寄生虫疟疾疫苗（辐射减毒子孢子（RAS））被用作模型系统，以建立由通过蚊虫叮咬传递的寄生虫诱导的归巢受体特征，为疟疾疫苗开发者提供理想归巢受体的基准。这种免疫方案导致抗原特异性B细胞和CD8 T细胞的启动，使其主要归巢至皮肤和次级淋巴器官的T/B细胞区室。然而，感染活子孢子会触发肝脏和皮肤归巢受体的上调，这表明减毒子孢子与活子孢子提供的信号存在差异。这是关于子孢子印记归巢途径的首次报道，令人惊讶的是，它还指出活寄生虫提供了额外的、尚未确定的信号，这些信号促使淋巴细胞归巢至肝脏。数据还证明了该方法在评估疫苗制剂将抗原特异性淋巴细胞导向最相关解剖部位的潜力方面的实用性，从而可能影响疫苗效力。
