Ballet Romain, Emre Yalin, Jemelin Stéphane, Charmoy Mélanie, Tacchini-Cottier Fabienne, Imhof Beat A
Department of Pathology and Immunology, Centre Médical Universitaire, University of Geneva, Geneva, Switzerland.
Department of Biochemistry, and WHO Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.
PLoS Pathog. 2014 Dec 4;10(12):e1004550. doi: 10.1371/journal.ppat.1004550. eCollection 2014 Dec.
The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C) on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs) from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1) response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2) response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.
树突状细胞募集至感染部位并迁移至淋巴结对于抗原加工以及向T细胞呈递抗原而言至关重要。在本研究中，我们发现，对内皮细胞上的连接黏附分子C（JAM-C）进行抗体阻断后，JAM-C从连接处脱离，且在硕大利什曼原虫感染后血管通透性增加。这对免疫反应的结果产生了多重影响。在抗性C57BL/6小鼠和易感BALB/c小鼠中，我们发现从血液迁移至感染部位的固有免疫细胞数量更多。随后，树突状细胞（DC）从皮肤向引流淋巴结的迁移也得到改善，从而增强了适应性免疫反应的诱导。在C57BL/6小鼠中，硕大利什曼原虫注射后进行JAM-C阻断导致以干扰素-γ为主导的辅助性T细胞1（Th1）反应增强，皮肤损伤和寄生虫负荷减轻。相反，抗JAM-C治疗在疾病加重的BALB/c小鼠中增加了白细胞介素-4驱动的辅助性T细胞2（Th2）反应。总体而言，我们的结果表明，JAM-C阻断可精细调节固有细胞迁移，并加速随后针对硕大利什曼原虫的免疫反应，而不改变辅助性T细胞反应的类型。
