Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting cells (APCs). In this study we evaluated whether treatment of murine bone marrow HSPCs with a TLR2 or Dectin-1 ligand impacts the antigen presenting capacity of APCs derived from them in vitro. Following activation with microbial ligands or Candida albicans yeasts, APCs derived from TLR2/Dectin-1-programed HSPCs exhibit altered expression of MHCII (signal 1), co-stimulatory molecules (CD40, CD80 and CD86; signal 2) and cytokines (TNF-α, IL-6, IL-12 p40 and IL-2; signal 3). Moreover, APCs derived from TLR2/Dectin-1-programed HSPCs prime enhanced Th1 and Th17 responses, which are important for antifungal defense, in CD4 T cell cocultures. Overall, these results demonstrate for the first time that microbial detection by bone marrow HSPCs can modulate the adaptive immune response by inducing the production of APCs with an altered phenotype.

中文翻译：

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小鼠造血干细胞和祖细胞中的TLR2和Dectin-1信号影响它们产生的抗原呈递细胞激活CD4 T细胞的能力。

通过在造血干细胞和祖细胞（HSPC）上表达的模式识别受体（PRR）进行的微生物识别不仅可以激活骨髓生成，还可以编程它们产生的单核细胞和巨噬细胞的功能。例如，HSPC程序设计的改变改变了衍生自它们的巨噬细胞产生炎性细胞因子的能力。虽然暴露于TLR2激动剂的HSPC产生耐受的巨噬细胞（促炎细胞因子的产生较低），但用Dectin-1配体处理的HSPC产生训练过的巨噬细胞（促炎细胞因子的产生较高）。但是，关于将HSPC暴露于微生物对抗原呈递细胞（APC）功能的影响尚无定论。在这项研究中，我们评估了用TLR2或Dectin-1配体治疗鼠类骨髓HSPC是否会影响其体外衍生的APC的抗原呈递能力。用微生物配体激活后或白色念珠菌酵母，从TLR2 / Dectin-1编程的HSPC衍生的APC表现出MHCII（信号1），共刺激分子（CD40，CD80和CD86;信号2）和细胞因子（TNF-α，IL-6， IL-12 p40和IL-2；信号3）。此外，在CD4 T细胞共培养物中，由TLR2 / Dectin-1编程的HSPC衍生的APC可引发增强的Th1和Th17反应，这对于抗真菌防御至关重要。总体而言，这些结果首次证明了骨髓HSPC的微生物检测可以通过诱导表型改变的APC的产生来调节适应性免疫反应。