C-type lectin-mediated training and polarization of bovine monocytes and macrophages

先天免疫记忆描述了先天免疫细胞对病原体或微生物相关分子模式（PAMP/MAMP）的反应不同的现象，如果它们先前与这种PAMP/MAMP或其他病原体接触过。较强的次级反应是训练效果的结果，称为训练的先天免疫。诱导训练的先天免疫被认为是一个有前途的预防概念。为了使这一概念对奶牛有用，有关相关和可训练的免疫细胞，单核细胞和单核细胞衍生的巨噬细胞的生物学的基本知识是至关重要的。目前尚不清楚不同泌乳期和繁殖期奶牛的激素谱和循环血清代谢产物在多大程度上影响单核细胞-巨噬细胞分化和极化，以及这如何指导对PAMP/MAMP的反应和诱导先天免疫训练。因此，拟议的项目旨在分析牛单核细胞亚群的组成，它们的转录组，它们的C型凝集素受体（CLRs）的表达模式和它们的可训练性的牛在妊娠后期和泌乳中期的β-配体。这将通过对单核细胞和巨噬细胞在配体诱导的先天免疫训练后的表观遗传修饰和效应子功能的机制分析来补充。CLR介导的训练和单核细胞-巨噬细胞分化和极化发生在奶牛的生命中心阶段，以检查基于先天免疫训练的免疫调节策略何时显示有效性。该项目将提供牛单核细胞和巨噬细胞功能的CLR依赖性调节的见解。研究结果可为奶牛围产期传染病的预防和生产性能适应性免疫调节方案的合理设计提供参考。

Innate immune memory describes the phenomenon that innate immune cells respond differently towards a pathogen or microbe-associated molecular pattern (PAMP/MAMP) if they have previously been in contact with this PAMP/MAMP or other pathogens. The stronger secondary response is the result of a training effect and is called trained innate immunity. Induction of trained innate immunity is considered a promising prophylactic concept. To render this concept useful for dairy cattle, basic knowledge about the biology of relevant and trainable immune cells, the monocytes and monocyte-derived macrophages, is crucially needed. It is still unknown to what extent the hormonal profile and circulating serum metabolites of cows in different lactation and reproduction phases affect the monocyte-macrophage differentiation and polarization, and how this guides the response towards PAMPs/MAMPs and the induction of innate immune training. Thus, the proposed project aims at analyzing the composition of bovine monocyte subpopulations, their transcriptome, their expression pattern of C-type lectin receptors (CLRs) and their trainability by CLR ligands of cows in late pregnancy and mid-lactation. This will be complemented by mechanistic analyses of epigenetic modifications and effector functions of monocytes and macrophages after CLR ligand-induced innate immune training. CLR-mediated training and monocyte-macrophage differentiation and polarization takes place during the central life phases of dairy cows to examine when innate immune training-based immunomodulatory strategies show effectiveness. The project will provide insights into CLR-dependent modulation of bovine monocyte and macrophage functions. The results may be transferrable to the prophylaxis of peripartal infectious diseases and the rational design of performance-adapted immune modulatory concepts in dairy cows.