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

Subject Area Veterinary Medical Science
Term since 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 517550756
 
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.
DFG Programme Research Grants
 
 

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