Abstract
Mastitis, one of the most costly diseases in dairy ruminants, is an inflammation of the mammary gland caused by pathogenic infection. The mechanisms of adaptive immunity against pathogens in mastitis have not been fully elucidated. To investigate T helper cell-mediated adaptive immune responses, we established a mastitis model by challenge with an inoculum of 4 × 106 colony-forming units of Staphylococcus aureus in the mammary gland of lactating mice, followed by quantification of bacterial burden and histological analysis. The development of mastitis was accompanied by a significant increase in both Th17 and Th1 cells in the mammary gland. Moreover, the relative expression of genes encoding cytokines and transcription factors involved in the differentiation and function of these T helper cells, including Il17, Rorc, Tgfb, Il1b, Il23, Ifng, Tbx21, and Il12, was greatly elevated in the infected mammary gland. IL-17 is essential for neutrophil recruitment to infected mammary gland via CXC chemokines, whereas the excessive IL-17 production contributes to tissue damage in mastitis. In addition, a shift in T helper cell polarization toward Th2 and Treg cells was observed 5 days post-infection, and the mRNA expression of the anti-inflammatory cytokine Il10 was markedly increased at day 7 post-infection. These results indicate that immune clearance of Staphylococcus aureus in mastitis is facilitated by the enrichment of Th17, Th1 and Th2 cells in the mammary gland mediated by pro-inflammatory cytokine production, which is tightly regulated by Treg cells and the anti-inflammatory cytokine IL-10.
Highlights
Mastitis is one of the most prevalent diseases in dairy ruminants worldwide, with an incidence ranging from 10 to 74% in dairy cows and 9 to 50% in dairy goats [1,2,3,4]
The presence of T helper and T killer cells confirmed the involvement of T cells in the adaptive immune response against S. aureus infection in the udder
The percentages of T killer cells were significantly higher in both the spleen and mammary gland at 3 days post-infection (Fig 2B and 2D), and the highest percentage of T killer cells (30.00%) was detected in local inflammatory lesions at day 5 post-challenge. These data indicate that both T helper and T killer cells contribute to the adaptive immune response against S. aureus infection in a murine model of mastitis
Summary
Mastitis is one of the most prevalent diseases in dairy ruminants worldwide, with an incidence ranging from 10 to 74% in dairy cows and 9 to 50% in dairy goats [1,2,3,4]. Mastitis occurs in other animals, including camel, buffalo, cats and dogs [5,6,7,8]. Mastitis causes considerable economic losses due to decreases in the quantity and quality of milk as well as early culling of dairy animals and high treatment costs, which are estimated to be $2 billion annually in the US alone [9]. To minimize this economic damage and maintain animal health, antibiotic treatments are important for mastitis therapy [10]. Public health concerns, including antibiotic residues in food for human consumption and the occurrence of drug-resistant
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