Department of Chemical Engineering, University of Michigan, G045W NCRC B28, 2800 Plymouth Rd, Ann Arbor, MI, 48109-2136, USA.
Department of Microbiology and Immunology, University of Michigan Medical School, 1150W Medical Center Drive, 5641 Medical Science II, Ann Arbor, MI, 48109-5620, USA.
Sci Rep. 2022 Dec 1;12(1):20731. doi: 10.1038/s41598-022-24516-8.
Some persistent infections provide a level of immunity that protects against reinfection with the same pathogen, a process referred to as concomitant immunity. To explore the phenomenon of concomitant immunity during Mycobacterium tuberculosis infection, we utilized HostSim, a previously published virtual host model of the immune response following Mtb infection. By simulating reinfection scenarios and comparing with data from non-human primate studies, we propose a hypothesis that the durability of a concomitant immune response against Mtb is intrinsically tied to levels of tissue resident memory T cells (Trms) during primary infection, with a secondary but important role for circulating Mtb-specific T cells. Further, we compare HostSim reinfection experiments to observational TB studies from the pre-antibiotic era to predict that the upper bound of the lifespan of resident memory T cells in human lung tissue is likely 2-3 years. To the authors' knowledge, this is the first estimate of resident memory T-cell lifespan in humans. Our findings are a first step towards demonstrating the important role of Trms in preventing disease and suggest that the induction of lung Trms is likely critical for vaccine success.
一些持续性感染会提供一定程度的免疫力，从而防止同一病原体的再次感染，这一过程被称为伴随免疫。为了探索结核分枝杆菌感染过程中伴随免疫的现象，我们利用 HostSim，这是一种先前发表的结核分枝杆菌感染后免疫反应的虚拟宿主模型。通过模拟再感染情况，并与非人类灵长类动物研究的数据进行比较，我们提出了一个假设，即针对 Mtb 的伴随免疫反应的持久性与初次感染期间组织驻留记忆 T 细胞 (Trms) 的水平内在相关，循环 Mtb 特异性 T 细胞起着次要但重要的作用。此外，我们将 HostSim 再感染实验与抗生素前时代的观察性结核病研究进行比较，预测人类肺组织中驻留记忆 T 细胞寿命的上限可能为 2-3 年。据作者所知，这是对人类驻留记忆 T 细胞寿命的首次估计。我们的发现是证明 Trms 在预防疾病方面的重要作用的第一步，并表明诱导肺 Trms 可能对疫苗成功至关重要。
