Immunity and mastitis - Some new ideas for an old disease

Because the bovine mammary gland is constantly challenged by a variety of contagious and environmental pathogens, maintenance of mammary health may be best thought of in terms of immune defense (responsiveness) rather than strict resistance to mastitis-causing organisms. Basic aspects of the physical, biochemical, and cellular defense components of the bovine mammary gland defense system are well known and described in numerous reviews [1-8]. Summarizing across these reviews, one comes to the definitive conclusion that for most types of bovine mastitis, phagocytic neutrophils-facilitated in their immune defense work by pathogen-reactive opsonizing antibodies-are the key immune effectors in the battle between host and mastitis-causing bacteria. Blood vessel endothelial cells, mammary epithelial cells, milk macrophages, and T and B lymphocytes of the peripheral immune system also play important roles in the local inflammatory response, helping to recruit opsonizing antibodies and neutrophils from blood into milk for rapid phagocytic clearance of the opsonized pathogens. Indeed, it is clear that this inflammatory response effectively deals with most intramammary pathogens on a regular basis because mammary quarters come into contact with mastitis-causing pathogens much more frequently than mastitis occurs. When the inflammatory events that should lead to rapid antibody and neutrophil recruitment into the gland fail to occur or occur too slowly, however, health of the gland is put in jeopardy and animals develop clinical mastitis that can be acute and severe or more chronic in nature. The basic physiologic factors, molecular mechanisms, and gene systems responsible for mastitis susceptibility in dairy cows are almost completely unknown and this has seriously impeded our ability to substantially improve overall resistance to mastitis through therapies, vaccination programs, and genetic selection schemes. A relatively new area of scientific discovery called animal functional genomics is, gradually allowing researchers to solve the puzzles of disease susceptibility and resistance states. For example, immunogenomics research is beginning to provide clues about the complexity of changes in gene systems expressed in neutrophils and other leukocytes of mastitis-susceptible periparturient cows [9-11]. Results of this type of research offer the hope of giant leaps toward a clear identification of molecular genetic variation and potential gene targets for therapies and immune manipulations that could significantly reduce the risk of clinical mastitis in traditionally susceptible cows. The intent of this article is not to reiterate all general aspects of bovine host defense against intramammary infections because these have been so well reviewed by others. Instead, the goal of this article is to bring to the reader a wider appreciation of some key molecules that are now known to regulate the neutrophil defense system against mastitis-causing pathogens. This discussion will be supplemented with some new ideas about what might be happening to the neutrophil defense system in highly susceptible periparturient cows, including some preliminary functional genomics data from the authors' recent studies on periparturient neutrophils.