CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection,Immunity

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CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection
Immunity ( IF 25.5 ) Pub Date : 2024-08-29 , DOI: 10.1016/j.immuni.2024.08.002
Joshua D Bromley ₁ , Sharie Keanne C Ganchua ₂ , Sarah K Nyquist ₃ , Pauline Maiello ₄ , Michael Chao ₅ , H Jacob Borish ₂ , Mark Rodgers ₂ , Jaime Tomko ₂ , Kara Kracinovsky ₂ , Douaa Mugahid ₅ , Son Nguyen ₆ , Qianchang Dennis Wang ₇ , Jacob M Rosenberg ₅ , Edwin C Klein ₈ , Hannah P Gideon ₂ , Roisin Floyd-O'Sullivan ₆ , Bonnie Berger ₉ , Charles A Scanga ₂ , Philana Ling Lin ₁₀ , Sarah M Fortune ₅ , Alex K Shalek ₁₁ , JoAnne L Flynn ₂

Affiliation

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.
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; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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.
Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA.
Division of Laboratory Animal Research, University of Pittsburgh, Pittsburgh, PA, USA.
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

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.

中文翻译：

CD4+ T 细胞重新连接肉芽肿细胞结构和调节网络，以促进 Mtb 再感染后的免疫调节

免疫启动——在先前感染或接种疫苗的情况下——引发对随后的结核分枝杆菌（Mtb）感染的保护性反应。然而，原发性 Mtb 感染后肺细胞环境中发生的变化及其对再感染保护的贡献仍然知之甚少。使用非人灵长类动物再感染模型中的临床和微生物学终点，我们证明先前的 Mtb 感染对随后的 Mtb 暴露产生了持久的保护反应，并且是 CD4 + T 细胞依赖性的。通过分析原发感染、再感染和再感染 CD4+ T 细胞耗竭肉芽肿的数据，我们发现再感染期间 CD4+ T 细胞的存在导致肺环境炎症性降低，其特征是髓系细胞中 CD8+ T 细胞重编程、中性粒细胞减少和 1 型免疫信号减弱。这些结果为开发疫苗和疗法开辟了途径，这些疫苗和疗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。

更新日期：2024-08-29

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