Immunology-based approaches to strengthen udder health in dairy cows: a new perspective on mastitis control
Bovine mastitis is the lead cause of economic loss disease in the dairy industry, responsible for and accounts for up to 70% of antimicrobial use on dairy farms. In light of rising concerns about antimicrobial resistance, immunological strategies are being explored to optimize dairy cows’ immune responses and reduce reliance on conventional antimicrobial treatments. First, our research focused on the immune checkpoint molecules Programmed Death-1 (PD-1) and Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) in T lymphocytes during the periparturient period, investigating associations with new intramammary infections during this critical period of the cows’ lives. Furthermore, we successfully developed a novel immortalized keratinocyte cell line from the bovine teat canal to study the first line of defense against mastitis-causing pathogens. These innovative approaches offer promising alternatives to reduce antibiotic dependence in udder health management.
Immune checkpoints are essential regulatory mechanisms of the immune system that play a vital role in maintaining self-tolerance and modulating the duration and amplitude of immune responses. While these pathways are crucial for preventing immune-driven pathology, they can also limit the immune system’s capacity to effectively clear infections. The recent success of immune checkpoint blockade in cancer therapy highlights the significant potential of targeting these pathways, suggesting that such strategies could be equally effective in the prevention and treatment of a broad range of infectious diseases. Programmed Death-1 and CTLA-4 are among the most well-characterized immune checkpoint proteins. The importance of these immune checkpoints lies in their ability to regulate T cell activation and function.
In this context, we investigated the relationship between the expression of immune checkpoint proteins, PD-1 and CTLA-4, in blood T lymphocytes of dairy cows during the periparturient period and the incidence of new intramammary infections (IMIs) during early lactation. Notably, our findings revealed that higher expression of PD-1 at 14 days prior to calving and of CTLA-4 on the day of parturition are associated with an increased incidence of IMIs caused by major pathogens within the first month of lactation. Furthermore, elevated expression of CTLA-4 on the day of calving was also associated with the persistence of IMIs.
The teat canal is predominantly composed of keratinocytes arranged in a stratified squamous epithelium that undergoes constant keratinization and sloughing. This dynamic barrier plays a critical role in preserving structural integrity while providing essential immunological surveillance to prevent the entry of mastitis-causing pathogens. Gaining a deeper understanding of the specific roles keratinocytes play in the bovine teat canal could offer invaluable insights into the early stages of host-pathogen interactions during mastitis pathogenesis. Such knowledge has the potential to lay the foundation for developing novel strategies aimed at enhancing natural resistance to intramammary infections, ultimately improving udder health and milk quality in dairy cattle. However, the precise mechanisms and functions of keratinocytes in immunological surveillance remain largely unexplored. To bridge this gap, a novel immortalized keratinocyte cell line from the teat canal of the mammary gland was established. This cell line provides a powerful tool for investigating the immunological functions of the teat canal in bovine mastitis and could pave the way for innovative strategies in disease prevention and treatment.
Immunological strategies that optimize the immune response in dairy cows are emerging as a new paradigm for udder health and for the prevention of intramammary infections, offering promising alternatives to reduce reliance on antibiotics.
Ana Claudia Dumont Oliveira graduated as a veterinarian in 2012 from the Federal University of Minas Gerais, Brazil. Since then, she has worked as a veterinary advisor specializing in udder health and mastitis. With a passion for science communication, particularly in dairy ruminant mastitis and milk quality, she co-founded the company MilkCare. Ana Claudia completed her master’s degree in 2018 at the same institution. She earned her doctorate at the University of São Paulo (Brazil) under the mentorship of Prof. dr. Fernando Nogueira de Souza, focusing on bovine mammary gland immunology. During this time, she also undertook a one-year internship with M-teamUGent in Belgium.
