Dysregulated Efferocytosis and Immune Microenvironment in High Somatic Cell Count Dairy Cows

Milk cells are mirrors of mammary health and immune responses in dairy cows. However, their specific physiological or pathological significance in cows with high somatic cell count (SCC) remains poorly understood. Dysregulation of milk cell physiology may contribute to inflammatory responses and impact mammary health and milk production. By investigating the composition and function of milk cells in high and low SCC cows, our study aimed to identify SCC-associated biological processes in the mammary gland. Sixteen animals were divided as two groups, SCC-h group (n = 8, milk SCC > 200 × 10³/mL) and SCC-l group (n = 8, milk SCC < 100 × 10³/mL). The milk performance traits of dairy cows were assessed, and RNA sequencing of milk cells was conducted. Metabolomic analysis was performed to identify 'find-me' signals associated with efferocytosis. The expression patterns of genes involved in apoptotic and non-apoptotic cell death, actin remodelling and efferocytosis were analysed. The protein levels of inflammatory and anti-inflammatory genes and nuclear receptors were determined. The immune microenvironment in milk cells was also dissected to understand the dysregulation in high SCC cows. The results showed increased expressions of key genes associated with apoptosis, necroptosis and pyroptosis in the high SCC group. However, the 'find-me' signals and 'eat-me' signals in the high SCC group were reduced compared with the low SCC group. Therefore, the protein levels of IL-1β and nuclear factor kappa B subunit 1 (NFκB1) levels were increased, whereas the protein level of peroxisome proliferator-activated receptor γ (PPARγ) was decreased in high SCC group. These results demonstrated an enhanced pro-inflammatory signalling and altered immune microenvironment of milk cells in high SCC group. The high SCC group showed higher proportions of various types of immune cells, including dendritic cell, neutrophil and CD8⁺ T cell, indicating a pro-inflammatory immune microenvironment. Our study highlights the dysregulation of efferocytosis and immune microenvironment in milk cells of high SCC cows, potentially contributing to chronic inflammation and impaired mammary gland health. Reviving proper efferocytic function and rebalancing the immune microenvironment are essential for enhancing disease management and improving dairy cow welfare and productivity. Understanding the significance of milk cells in udder health can facilitate targeted interventions to optimise milk production and maintain mammary health in dairy farming.