Compromised neutrophil function and bovine E. coli mastitis: is C5a the missing link?

During early lactation, dairy cow are prone to developing severe mastitis in responses to intramammary Escherichia coli infections. These severe inflammatory responses have been correlated with reduced neutrophil function during the periparturient period. However, the causative mechanism of neutrophil dysfunction has not been elucidated. Studies in murine sepsis models have shown that during sepsis neutrophils are functionally paralysed due to the presence of high concentrations of complement factor 5a (C5a). In this review, we hypothesize that C5a as a critical early mediator in the development of severe E. coli mastitis. Furthermore, preliminary data suggest that crosstalk between C5a and TLR4 signalling in neutrophils may provide a positive feedback mechanism that may be involved in the pathogenesis of a severe mastitis response. Finally, we focus on the therapeutic potential of disrupting the C5a signalling pathway as an important strategy for treatment of severe E. coli mastitis in dairy cattle.