Abstract:
Prophylactic vaccination strategies designed to prevent diseases caused by pathogens using the phagolysosome of innate immune cells as a site of intracellular replication and survival have been largely ineffective. These include Mycobacterium tuberculosis (Mtb), Leishmania spp., and Cryptococcus spp. These failed strategies have traditionally targeted CD4+ T helper (Th) 1 cell-mediated immune memory, deeming it crucial for vaccine efficacy. This failure warrants an investigation of alternative mediators of protection. Here, we suggest three novel approaches to activate phagocytic cells prior to or at the time of infection. We hypothesize that preventing the formation of the pathogen niche within the phagolysosome is essential for preventing disease, and a greater emphasis on the timing of phagocyte activation should generate more effective prophylactic treatment options.
摘要:
旨在使用先天免疫细胞的吞噬溶酶体作为细胞内复制和存活位点来预防由病原体引起的疾病的预防性疫苗接种策略在很大程度上是无效的。这些包括结核分枝杆菌(Mtb),利什曼原虫。,和隐球菌属。这些失败的策略传统上靶向CD4+T辅助(Th)1细胞介导的免疫记忆,认为它对疫苗效力至关重要。这种失败需要对保护的替代调解人进行调查。这里,我们提出了三种在感染前或感染时激活吞噬细胞的新方法。我们假设,防止在吞噬溶酶体内形成病原体生态位对于预防疾病至关重要,更加强调吞噬细胞激活的时机应该会产生更有效的预防性治疗选择。