Rincon Jaimar C, Wang Dayuan, Polcz Valerie E, Barrios Evan L, Dirain Marvin L, Ungaro Ricardo F, Nacionales Dina C, Zeumer-Spataro Leilani, Xiao Feifei, Efron Philip A, Moldawer Lyle L, Cai Guoshuai, Larson Shawn D
Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, 1600 SW Archer Road, P.O. Box 100119, Gainesville, FL, 32610 - 0019, USA.
Division of Pediatric Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
Mol Med. 2025 Apr 30;31(1):159. doi: 10.1186/s10020-025-01179-5.
Neonates, especially those born prematurely, are highly vulnerable to infection-induced mortality. Numerous observational and immunological studies in newborns have shown that live attenuated vaccines have beneficial, non-specific effects (NSEs) against secondary infections to unrelated pathogens. These beneficial effects have been attributed to trained immunity, and emergency granulopoiesis plays an essential role. However, trained immunity has been shown to affect multiple myeloid subsets and how trained immunity influences the host protective response is still undefined. Here we show that Bacillus-Calmette-Guérin (BCG) vaccination improves survival to polymicrobial sepsis by simultaneously reprogramming broad aspects of myelopoiesis. Specifically, BCG vaccination expands multiple myeloid subsets, including the lineage (Lin)Sca- 1c-kit (LSK) and granulocytic-macrophage progenitors (GMPs), and increases CD11bGr1 cell number, as well as their oxidative metabolism and capacity to stimulate T-cell proliferation in response to sepsis. Single-cell RNA sequencing of neonatal splenocytes suggests that BCG-vaccination changes the broad transcriptional landscape of multiple myeloid subsets. The result is the maturation of various neutrophil and monocyte subsets, stimulation of antimicrobial processes, and suppression of inflammatory pathways and myeloid-derived suppressor cell transcription. These findings reveal that BCG administration early after birth fundamentally reorganizes the myeloid landscape to benefit the subsequent response to polymicrobial infection.
新生儿，尤其是早产儿，极易因感染而死亡。众多针对新生儿的观察性研究和免疫学研究表明，减毒活疫苗对无关病原体的继发感染具有有益的非特异性效应（NSEs）。这些有益效应归因于训练有素的免疫，而应急粒细胞生成起着至关重要的作用。然而，已证明训练有素的免疫会影响多个髓系亚群，且训练有素的免疫如何影响宿主的保护性反应仍不明确。在此，我们表明卡介苗（BCG）接种通过同时重新编程髓系造血的多个方面，提高了对多重微生物败血症的存活率。具体而言，卡介苗接种可扩大多个髓系亚群，包括谱系（Lin）Sca-1c-kit（LSK）和粒细胞-巨噬细胞祖细胞（GMPs），并增加CD11bGr1细胞数量，以及它们的氧化代谢和响应败血症刺激T细胞增殖的能力。对新生小鼠脾细胞进行单细胞RNA测序表明，卡介苗接种改变了多个髓系亚群的广泛转录格局。结果是各种中性粒细胞和单核细胞亚群成熟，抗菌过程受到刺激，炎症途径和髓系来源的抑制性细胞转录受到抑制。这些发现表明，出生后早期接种卡介苗能从根本上重组髓系格局，有利于随后对多重微生物感染的反应。
