Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Duchossois Family Institute, University of Chicago, Chicago, IL, 60606, USA.
Nat Commun. 2020 Sep 8;11(1):4475. doi: 10.1038/s41467-020-18248-4.
Tissue resident memory CD8 T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.
组织驻留记忆 CD8+T 细胞（Trm）在病原体进入部位随时准备被重新激活，并为黏膜表面提供最佳保护。肠道是许多感染性病原体的入口；然而，迄今为止，针对该部位增强 Trm 反应的具体策略仍缺乏。在这里，我们提出 TMDI（短暂微生物组耗竭增强免疫接种），这是一种利用抗生素治疗暂时抑制微生物组介导的定植抵抗，并有利于高浓度口服传递的李斯特菌单核细胞增生症株的方法携带选择的抗原。通过增加局部趋化梯度和抗原负荷，该方法产生了大量功能、抗原特异性的肠道 Trm，最终增强了对再次感染的保护作用在小鼠中。我们认为，TMDI 是一种有用的模型，可以剖析在肠道中获得最佳 Trm 反应的要求，也是设计新型黏膜疫苗接种方法的潜在平台。
