At epithelial barriers such as the skin, respiratory, intestinal and urogenital tracts, the production of IL-17A is important in host defense against extracellular bacteria. Recently, we obtained evidence for an important contribution of IL-17A to mammary gland (MG) protection against bacterial infection:
1) We found expression of the genes coding the IL-17A receptor complex in mammary tissue and mammary epithelial cells (MEC). These cells responded to bovine IL-17A by producing chemokines and by expressing antibacterial peptides.
2) In cows systemically immunized with ovalbumin, we showed that the production of IL-17A and INF-γ by circulating CD4+ T lymphocytes correlated with the neutrophilic inflammation which followed an intramammary challenge with ovalbumin.
3) In vitro experiments indicated that MEC responses to agonists of TLR2 and TLR4 or to live E. coli were amplified by IL-17A. Paralleling this result, the simultaneous injection of E. coli lipopolysaccharide with antigen into the MG of ovalbumin-sensitized cows induced a synergistic reaction.
4) By using a mouse model of Escherichia coli mastitis, we showed that depletion of IL-17A correlated with an increased bacterial colonization, whereas intramammary infusion of IL-17A at the onset of infection was associated with markedly decreased bacterial numbers while neutrophil recruitment was increased.
5) The production of IL-17A in the mammary tissue following antigenic challenge with ovalbumin or E. coli infection of the MG was substantiated by immunohistochemistry. Following induced infection of the bovine MG with E. coli, IL-17A concentration in milk and IL17A expression in mammary tissue increased significantly.
Taken together these findings indicate that IL-17A is likely to contribute to the innate and adaptive immune defenses of the MG against infection by mastitis-causing coliform bacteria. Harnessing the IL-17 immune axis in the MG through vaccination opens up new opportunities to improve MG protection against infection.