Systemic effects of mastitis in the dairy cow : identifying mechanisms underlying impaired lactation in non-inflamed glands
Authors:   , Shangraw Erin 
Published: December 2023

Efficient milk production is temporarily compromised during the inflammatory response to lipopolysaccharide (LPS). Generally, the most severe losses are localized to individual mammary glands with overt cases of mastitis. However, systemic inflammation arising from an inflamed gland can negatively impact lactation in healthy neighboring glands. This interdependence between glands highlights the importance of systemic inflammation in regulating lactation, yet the underlying mechanisms and mediators remain poorly understood. To determine these systemic mechanisms, paired cows were randomly assigned to LPS treatment (T) or saline control (C). Within each treatment, two ipsilateral quarters received one of 2 intramammary sub-treatments: in T cows, infusion of 50 [micrograms] LPS (T-L) or saline (T-S); in C cows, infusion of saline (C-S) or no infusion (C-N). Front quarters were sampled for milk production and composition while rear quarters were biopsied at 0, 3, and 12 h, relative to infusions. Mammary tissue from 3 and 12 h biopsies was then subjected to RNA sequencing. Results from milk confirmed that LPS induced a characteristic immune response, with a local increase in milk somatic cells and total protein concentrations only in T-L quarters. In comparison, components associated with lactation were affected in both T-L and T-S quarters, with concentrations of milk fat and lactose being lower by 3 and 12 h post-infusion, respectively. Further, milk yields declined steadily over 24 h with similar losses in both T-L and T-S quarters. Induction of transient fever at 3 h, followed by changes in plasma antioxidant capacity and glucose concentrations, provided additional evidence of systemic responses to inflammation. Collectively, these results confirmed that localized mastitis affected neighboring glands and demonstrated that each milk component was affected by unique time- and treatment- dependent effects. Analyzing changes in the mammary transcriptome provided further insight into the regulation of the immune response and lactation during mastitis. Most genes were differentially expressed (DE) only in T-L glands and were associated with pro-inflammatory, cell signaling, and metabolic pathways. There was no direct link between expression of lactation-specific genes and hypogalactia or altered milk composition; however, genes unrelated to lactation were upregulated in T-S glands, suggesting that differential expression of other genes may have impacted lactation. At 3 h, the upregulation of negative feedback inhibitors of pro-inflammatory pathways in T-S tissue indicated unidirectional signaling from T-L to T-S glands, likely mediated by cytokines. Later, at 12 h, increased expression in T-S quarters of genes linked to one carbon metabolism and glucocorticoid stimulation indicated that other mediators may also impact milk production. From 3 to 12 h, expression of immune genes diminished in both glands despite increasing somatic cells in T-L quarters. Given the similar decline in quarter milk yields through 24 h, results suggested that an acute, transient inflammatory signal was sufficient to induce delayed effects on lactation. In summary, localized mastitis impaired lactation in non-inflamed, neighboring quarters through both direct and indirect actions of pro-inflammatory mediators.