Immunopathology of mastitis: insights into disease recognition and resolution.

Mastitis is an inflammation of the mammary gland commonly caused by bacterial infection. The inflammatory process is a normal and necessary immunological response to invading pathogens. The purpose of host inflammatory responses is to eliminate the source of tissue injury, restore immune homeostasis, and return tissues to normal function. The inflammatory cascade results not only in the escalation of local antimicrobial factors, but also in the increased movement of leukocytes and plasma components from the blood that may cause damage to host tissues. A precarious balance between pro-inflammatory and pro-resolving mechanisms is needed to ensure optimal bacterial clearance and the prompt return to immune homeostasis. Therefore, inflammatory responses must be tightly regulated to avoid bystander damage to the milk synthesizing tissues of the mammary gland. The defense mechanisms of the mammary gland function optimally when invading bacteria are recognized promptly, the initial inflammatory response is adequate to rapidly eliminate the infection, and the mammary gland is returned to normal function quickly without any noticeable clinical symptoms. Suboptimal or dysfunctional mammary gland defenses, however, may contribute to the development of severe acute inflammation or chronic mastitis that adversely affects the quantity and quality of milk. This review will summarize critical mammary gland defense mechanisms that are necessary for immune surveillance and the rapid elimination of mastitis-causing organisms. Situations in which diminished efficiency of innate or adaptive mammary gland immune responses may contribute to disease pathogenesis will also be discussed. A better understanding of the complex interactions between mammary gland defenses and mastitis-causing pathogens should prove useful for the future control of intramammary infections.

Pro-inflammatory and pro-apoptotic responses of TNF-α stimulated bovine mammary endothelial cells.

Coliform mastitis may be severe in periparturient cows due to enhanced expression of pro-inflammatory cytokines that contribute to disease pathogenesis. Tumor necrosis factor (TNF)-α is implicated with the severity of coliform mastitis by provoking inflammatory responses in affected tissues. The endothelium is an integral organ in regulating inflammatory responses and loss of endothelial integrity may be fatal. Studies in humans suggest that endothelial cell apoptosis may be a consequence of TNF-α exposure and contributes to the development of sepsis, however, its impact on bovine mammary endothelial cells (BMEC) is unknown. We sought to determine the inflammatory and apoptotic responses of primary BMEC exposed to TNF-α in vitro. Stimulation of endothelial monolayers with TNF-α resulted in significant increase of toll-like receptor 4, interleukin-6 and -8, and intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1 gene expression in a time-dependent manner. Caspase-8 and caspase-3 mRNA expression, as well as caspase enzyme activity, also increased significantly following TNF-α stimulation. Cell viability assessed by ATP activity and BMEC apoptosis determined by flow cytometry revealed no significant changes across time with TNF-α stimulation. Results suggest that TNF-α stimulation, at the dose used in this study, can elicit a pro-inflammatory response in BMEC, but not induce apoptosis. The impact of TNF-α on mammary vascular function and the subsequent impact on the pathophysiology of severe coliform mastitis warrant further investigation.

Metabolic factors affecting the inflammatory response of periparturient dairy cows.

Dairy cattle are susceptible to increased incidence and severity of disease during the periparturient period. Increased health disorders have been associated with alterations in bovine immune mechanisms. Many different aspects of the bovine immune system change during the periparturient period, but uncontrolled inflammation is a dominant factor in several economically important disorders such as metritis and mastitis. In human medicine, the metabolic syndrome is known to trigger several key events that can initiate and promote uncontrolled systemic inflammation. Altered lipid metabolism, increased circulating concentrations of non-esterified fatty acids and oxidative stress are significant contributing factors to systemic inflammation and the development of inflammatory-based diseases in humans. Dairy cows undergo similar metabolic adaptations during the onset of lactation, and it was postulated that some of these physiological events may negatively impact the magnitude and duration of inflammation. This review will discuss how certain types of fatty acids may promote uncontrolled inflammation either directly or through metabolism into potent lipid mediators. The relationship of increased lipid metabolism and oxidative stress to inflammatory dysfunction will be reviewed as well. Understanding more about the underlying cause of periparturient health disorders may facilitate the design of nutritional regimens that will meet the energy requirements of cows during early lactation and reduce the susceptibility to disease as a function of compromised inflammatory responses.

Impact of oxidative stress on the health and immune function of dairy cattle.

Oxidation and the production of free radicals are an integral part of aerobic metabolism. A variety of reactive oxygen species (ROS) are produced by normal metabolic processes and by certain leukocyte populations during defense against disease. Accumulated scientific evidence supports the concept that oxidative damage of tissues and cellular components are either a primary or secondary cause of many human diseases. Unfortunately, considerably less is known about how oxidative stress can affect veterinary health and well-being, particularly during times of high metabolic activity. The performance of high producing dairy cattle can be optimized to a certain extent by supplementing diets with optimal levels of micronutrients with antioxidant capabilities. However, oxidative stress continues to be a problem in transition cows. Innovative approaches are needed to enhance the antioxidant defense mechanisms of dairy cattle during times of increased metabolic demands.