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，如果它们以前与这种PAMP/MAMP或其他病原体接触过。较强的二次反应是训练效果的结果，被称为训练先天免疫。诱导训练先天免疫被认为是一种很有前途的预防概念。为了使这一概念对奶牛有用，对相关的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基础知识是至关重要的。奶牛不同哺乳期和生殖期的激素谱和循环血清代谢物在多大程度上影响单核-巨噬细胞的分化和极化，以及这如何指导对PAMPs/MAMPs的反应和诱导先天免疫训练，目前尚不清楚。因此，本项目旨在分析妊娠后期和哺乳中期奶牛单核细胞亚群的组成、转录组、c型凝集素受体（CLRs）的表达模式以及CLR配体对它们的可训练性。这将通过CLR配体诱导的先天免疫训练后单核细胞和巨噬细胞的表观遗传修饰和效应功能的机制分析来补充。clr介导的训练和单核巨噬细胞分化和极化发生在奶牛生命的中心阶段，以检验基于先天免疫训练的免疫调节策略何时显示有效。该项目将为clr依赖性牛单核细胞和巨噬细胞功能的调节提供见解。研究结果可用于奶牛围产期传染病的预防和性能适应性免疫调节概念的合理设计。

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.