Hypogalactia in mammary quarters adjacent to lipopolysaccharide-infused quarters is associated with transcriptional changes in immune genes

Infusion of lipopolysaccharides (LPS) into a mamma -ry gland can provoke inflammatory responses and im -pair lactation in both the infused gland and neighboring glands. To gain insight into the mechanisms controlling the spatiotemporal response to localized mastitis in lactating dairy cows, we performed RNA sequencing on mammary tissue from quarters infused with LPS, neighboring quarters in the same animals, and control quarters from untreated animals at 3 and 12 h postinfu-sion. Differences in gene expression were annotated to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Comparing mammary transcriptomes from all 3 treatments revealed 3,088 and 1,644 differen-tially expressed (DE) genes at 3 and 12 h, respectively. Of these genes, >95% were DE only in LPS-infused quarters and represented classical responses to LPS: inflammation, apoptosis, tissue remodeling, and altered cell signaling and metabolism. Although relatively few genes were DE in neighboring quarters (56 at 3 h; 74 at 12 h), these represented several common pathways. At 3 h, tumor necrosis factor (TNF), nuclear factor-kappa B, and nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathways were identi-fied by the upregulation of anti-inflammatory (NFK-BIA, TNFAIP3) and cell adhesion molecule (VCAM1, ICAM1) genes in neighboring glands. Additionally, at 12 h, several genes linked to 1-carb on and serine me-tabolism were upregulated. Some responses were also regulated over time. The proinflammatory response in LPS-infused glands diminished between 3 and 12 h, in-dicating tight control over transcription to re-establish homeostasis. In contrast, 2 glucocorticoid-responsive genes, FKBP5 and ZBTB16, were among the top DE genes upregulated in neighboring quarters at both time points, indicating potential regulation by glucocorti-coids. We conclude that a transient, systemic immune response was sufficient to disrupt lactation in neighbor-ing glands. This response may be mediated directly by proinflammatory factors from the LPS-infused gland or indirectly by secondary factors released in response to systemic inflammatory signals.

Automated summary

The infusion of LPS into the mammary gland causes inflammatory responses, apoptosis, and altered cell signaling and metabolism, affecting lactation in both the infused gland and neighboring glands. The immune response triggered by LPS may disrupt lactation in neighboring glands directly or indirectly through systemic inflammatory signals.