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Title: Innate Immune Response to Intramammary Mycoplasma bovis Infection

Author
item KAUF, ADAM - 1265-90-00
item ROSENBUSCH, RICARDO - IOWA STATE UNIVERSITY
item Paape, Max
item Bannerman, Douglas

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/30/2007
Publication Date: 6/22/2007
Citation: Kauf, A.C., Rosenbusch, R.F., Paape, M.J., Bannerman, D.D. 2007. Innate Immune Response to Intramammary Mycoplasma bovis Infection. Journal of Dairy Science. 90(7):3336-3348.

Interpretive Summary: Mycoplasma bovis characteristically establishes a chronic form of mastitis that is resistant to currently available therapeutics. Because the ability of bacteria to establish infection is governed, in part, by the nature of the immune/inflammatory response mounted by the host, this study characterized the innate immune response of cows to intramammary infection with M. bovis. By increasing our understanding of mammary gland host immune defense mechanisms, new therapeutics may be developed that can enhance and/or alter the immune response, thus, providing new treatments for curing bacterial infections currently resistant to approved antibiotics.

Technical Abstract: Mastitis caused by Mycoplasma bovis is a growing concern for the dairy industry. M. bovis intramammary infection commonly results in an untreatable case of chronic mastitis. The innate immune system is responsible for initial recognition of, and immediate host responses to, infectious pathogens. While the inflammatory response elicited during intramammary infection with such major mastitis pathogens as Escherichia coli or Staphylococcus aureus has recently been defined, little is known about the nature of the host response to intramammary M. bovis infection. The objective of the current study was to characterize the systemic and local innate immune response during experimentally-induced M. bovis mastitis. Ten Holstein cows were each infused in one quarter with M. bovis and studied for a 10 day period. Acute phase protein synthesis, which reflects one parameter of the systemic response to infection, was induced within 108 h of infection as evidenced by increased circulating levels of lipopolysaccharide binding protein and serum amyloid A. Transient neutropenia was observed from 84 - 168 h post-infection, whereas, a constant state of lymphopenia and thrombocytopenia were observed from 84 h until the end of the study. Milk somatic cell counts initially increased within 66 h of M. bovis infusion and remained elevated, relative to time 0 (baseline levels), for the remainder of study. Increased milk levels of BSA, which reflect increased permeability of the mammary epithelial-endothelial barrier, were evident within 78 h of infection and sustained from 90 h until the end of the study. Milk levels of several cytokines, including IFN-gamma, IL-1beta, IL-10, IL-12, TGF-alpha, and TNF-alpha, were elevated in response to infection over a period of several days, whereas, increases in milk IL-8 were of a more limited duration. Complement activation, reflected by increased milk levels of C5a, was also observed over several days. Despite the indication by these observed changes that the cows mounted a prolonged inflammatory response to M. bovis intramammary infection, all quarters remained infected throughout the study with persistently high levels of this bacterium. Thus, a sustained inflammatory response is not sufficient to eradicate M. bovis from the mammary gland and may reflect the host's ongoing struggle to clear this persistent pathogen.