GM-CSF Programs Hematopoietic Stem and Progenitor Cells During Candida albicans Vaccination for Protection Against Reinfection.
GM-CSF Programs Hematopoietic Stem and Progenitor Cells During Candida albicans Vaccination for Protection Against Reinfection.
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DOI：
10.3389/fimmu.2021.790309
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yáñez A
中科院分区：
文献类型：
--
作者：
Bono C;Guerrero P;Jordán-Pla A;Erades A;Salomonis N;Grimes HL;Gil ML;Yáñez A
需要更多的机制研究来揭示体内诱导训练免疫的隐藏细节。在这里，使用白色念珠菌活疫苗小鼠模型，我们表明，疫苗接种保护小鼠免受继发感染，并增加骨髓，特别是脾训练单核细胞的数量。此外，疫苗接种在感染期间早期扩增和重编程造血干细胞和祖细胞（HSPC），并将它们瞬时动员到脾脏以产生训练的巨噬细胞。经过训练的HSPC不仅针对髓样细胞产生而引发，而且还重新编程以产生更大量的促炎细胞因子以响应第二次攻击。此外，它们的过继转移足以保护小鼠免受再感染。从机制上讲，HSPC的自分泌GM-CSF活化是训练表型的原因，并且对于疫苗诱导的保护是必需的。我们的研究结果揭示了HSPC在训练免疫保护反应中的基本作用，为疾病预防和治疗开辟了新的途径。
More mechanistic studies are needed to reveal the hidden details of in vivo-induced trained immunity. Here, using a Candida albicans live vaccine mouse model we show that vaccination protects mice against a secondary infection and increases the number of bone marrow, and especially, splenic trained monocytes. Moreover, vaccination expands and reprograms hematopoietic stem and progenitor cells (HSPCs) early during infection and mobilize them transiently to the spleen to produce trained macrophages. Trained HSPCs are not only primed for myeloid cell production but also reprogramed to produce a greater amount of proinflammatory cytokines in response to a second challenge. Additionally, their adoptive transfer is sufficient to protect mice against reinfection. Mechanistically, autocrine GM-CSF activation of HSPCs is responsible for the trained phenotype and essential for the vaccine-induced protection. Our findings reveal a fundamental role for HSPCs in the trained immune protective response, opening new avenues for disease prevention and treatment.