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Title: The Toll-like receptor-4 (TLR-4) pathway and its possible role in the pathogenesis of Escherichia coli mastitis in dairy cattle.

item Deschepper, Stefanie
item De Ketelaere, Adelheid
item Bannerman, Douglas
item Paape, Max
item Peelman, Luc
item Burvenich, Christian

Submitted to: Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2007
Publication Date: 1/2/2008
Citation: De Schepper, S., De Ketelaere, A., Bannerman, D.D., Paape, M.J., Peelman, L., Burvenich, C. 2008. The Toll-like receptor-4 (TLR-4) pathway and its possible role in the pathogenesis of Escherichia coli mastitis in dairy cattle. Veterinary Research. 39(1):(article #5)1-23.

Interpretive Summary: Toll-like receptor 4 (TLR-4) has been identified as the putative transmembrane receptor of bacterial lipopolysaccharide (LPS), also referred to as endotoxin. LPS activation of TLR-4 initiates an intracellular signaling pathway leading to the production of pro-inflammatory cytokines and the upregulation of adhesion molecules. These latter responses enable the host to respond to infection and their impairment enables invading pathogens to overwhelm the immune system. The periparturient period in cattle is characterized by a general state of immunosuppression. The current manuscript provides evidence for a potential role of TLR-4 in contributing to this immunosuppressive state.

Technical Abstract: Mastitis is one of the most costly production diseases to the dairy industry and is caused by a wide array of microorganisms. In this review, we focus on the Gram-negative Escherichia coli infections that often occur at periods when the innate immune defense mechanisms are impaired (i.e., parturition through the first 60 days of lactation). There is substantial evidence demonstrating that during these periods, the expected influx of polymorphonuclear neutrophil leukocytes (PMN) into the mammary gland is delayed. Here, we provide some hypotheses on the potential mechanisms of action on how the disease may develop under circumstances of immunosuppression, and describe the potential involvement of the toll-like receptor-4 signal transduction pathway in the pathogenesis of E. coli mastitis. In addition, some ideas are proposed to help prevent E. coli mastitis and potentially other diseases caused by Gram-negative infections in general.