Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Graduate Program in Microbiology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
Immunity. 2024 Oct 8;57(10):2380-2398.e6. doi: 10.1016/j.immuni.2024.08.002. Epub 2024 Aug 29.
Immunological priming-in the context of either prior infection or vaccination-elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrated that prior Mtb infection elicited a long-lasting protective response against subsequent Mtb exposure and was CD4 T cell dependent. By analyzing data from primary infection, reinfection, and reinfection-CD4 T cell-depleted granulomas, we found that the presence of CD4 T cells during reinfection resulted in a less inflammatory lung milieu characterized by reprogrammed CD8 T cells, reduced neutrophilia, and blunted type 1 immune signaling among myeloid cells. These results open avenues for developing vaccines and therapeutics that not only target lymphocytes but also modulate innate immune cells to limit tuberculosis (TB) disease.
免疫启动——无论是先前的感染还是疫苗接种——会引发针对随后结核分枝杆菌（Mtb）感染的保护反应。然而，在初次 Mtb 感染后肺部细胞环境中发生的变化及其对再感染的保护作用仍知之甚少。在非人类灵长类动物再感染模型中，我们使用临床和微生物学终点证明，先前的 Mtb 感染引发了针对随后 Mtb 暴露的长期保护性反应，并且依赖于 CD4 T 细胞。通过分析初次感染、再感染和再感染-CD4 T 细胞耗竭性肉芽肿的数据，我们发现，再感染期间 CD4 T 细胞的存在导致肺部环境炎症程度降低，其特征是 CD8 T 细胞重新编程、中性粒细胞减少和髓样细胞中 1 型免疫信号转导减弱。这些结果为开发疫苗和治疗方法开辟了途径，这些方法不仅针对淋巴细胞，还调节先天免疫细胞以限制结核病（TB）疾病。
