GENOMIC AND IMMUNOLOGIC STRATEGIES TO IMPROVE MILK PRODUCTION EFFICIENCY AND CONTROL MASTITIS
Title: Cumulative physiological events modulate the inflammatory response of the bovine udder to Escherichia coli infections around parturition
| Burvenich, Christian - GHENT UNIVERSITY |
| Bannerman, Douglas |
| Peelman, Luc - GHENT UNIVERSITY |
| Kehrli Jr, Marcus |
| Paape, Max |
Submitted to: Meeting Abstract
Publication Type: Proceedings
Publication Acceptance Date: June 8, 2007
Publication Date: June 24, 2007
Citation: Burvenich, C., Bannerman, D.D., Lippolis, J.D., Peelman, L., Nonnecke, B.J., Kehrli Jr, M.E., Paape, M.J. 2007. Cumulative physiological events modulate the inflammatory response of the bovine udder to Escherichia coli infections around parturition. Proceedings of the Heifer Mastitis Conference. pp. 75-76. June 24-26, 2007. Ghent, Belgium. . Meeting Abstract.
A high proportion of intramammary coliform infections present at parturition develop disease characterized by severe inflammatory signs and sepsis during the first 60 to 70 d of the cow’s lactation.
In the lactating bovine mammary gland, the innate immune system plays a critical role in determining the outcome of these infections. During the last two decades, research has increased significantly on bovine mammary innate defense mechanisms in connection with the pathogenesis of coliform mastitis. Opportunistic infections with coliforms occur when the integrity of the host immune system is compromised by physical and physiological conditions that make the host more susceptible. The innate immune system of many periparturient cows seems to be immunocompromised. The cow’s defense system is unable to modulate the complex network of innate immune responses, leading to incomplete resolution of the pathogen and the inflammatory reaction. Periparturient immunosuppression is unlikely to be the result of a single physiological factor; more likely, several entities will be found to act in concert, with profound effects on the function of many organ systems of the periparturient dairy cow.
Neutrophils are key effector cells of the innate immune response to intramammary infection, and their function is influenced by many physiological events that occur during the transition period. During the last 30 yr, most efforts have been focused on neutrophil diapedesis, phagocytosis, and bacterial killing. How these functions modulate the clinical outcome of coliform mastitis, and how they can be influenced by hormones and metabolism has been the subject of intensive research worldwide and is the focus of this review. The afferent (sensing) arm of innate immunity, which enables host recognition of a diverse array of pathogens, is the subject of intense research interest and may contribute to the variable inflammatory response to intramammary infections during different stages of lactation.
Based on culmulative research identifying different factors that contribute to periparturient immunosuppression, the development of novel interventions that modulate the inflammatory response or enhance effector cell function or both may offer some promise for preventing or treating IMI in periparturient cows. Two main approaches can be used to modulate the innate resistance of the udder. The first is to enhance the efficacy of the efferent arm of innate immunity, that is, modulation of the attraction of competent phagocytes. It is generally accepted that the ability of neutrophils to ingest and kill bacteria is pivotal for the control of IMI. The second is to enhance fast detection of pathogens in the teat and udder cistern (afferent arm of innate immunity). Recognition of microbial molecular patterns by Toll-like receptors and other signaling pathways contribute to fast recognition. These receptors enhance expression of cytokines, in turn amplifying host responses to the pathogen. Such therapies must be achieved without causing exuberant inflammation that ultimately injures the mammary gland and increases mortality of the host.
At the moment, many mastitis research groups are searching to enhance resistance of the udder by enabling the mammary epithelium to secrete immune or antibacterial self and nonself (foreign) proteins. For example, proof of concept has been obtained with transgenic mice and cows. Interest is focused on, for example, lysostaphin (a prokaryotic protein that has potent anti-staphylococcal activity), lysozyme, lactoferrin, and soluble CD14. Inserting the gene for CD14 into the mammary gland will provide the CD14 necessary for recruitment of neutrophils and elimination of invading coliform mastitis-causing pathogens. Transgenic application of immune or antibacterial proteins is expected to unveil candidate genes whose promoter elements will enable temporal expression patterns. These genes could eventually be expressed through administration as food additives (certain fatty acids, for example, are known to be very active at the level of gene expression). Theoretically, inflammation-inducible expression constructs are superior to constitutive expression because the antibacterial proteins are only provided when needed.
However, most of the above mentioned novel interventions modulating the inflammatory response are still at an experimental stage. Meanwhile, the easiest prophylaxis today to prevent periparturient toxic mastitis is to provide periparturient cows not only with optimal hygiene conditions, but also with appropriate diets during the transition period and as few additional stress events as possible around calving. The metabolic demands of increasing milk secretion (protein and energy) affect the ability of the periparturient cow to manage its metabolism, as well as its ability to recover from an immunocompromised condition. Many theories exist on how better to manage the metabolic changes in the transition cow. Central to all these theories is to maximize feed intake and minimize serum NEFA levels around calving to maximize the profitability of the transition cow.