Stimulated expression of TNF-α and IL-8, but not of lingual antimicrobial peptide reflects the concentration of pathogens contacting bovine mammary epithelial cells

We examined if and how mammary epithelial cells (MECs) calibrate and confine the intensity of an inflammatory response elicited by different concentrations of mastitis pathogens. Therefore we quantified in primary bovine MEC the effect of different E. coli pathogen concentrations upon the abundance of mRNA molecules encoding factors of immune defence. Induced synthesis of the mRNAs encoding tumor necrosis factor alpha and interleukin 8 both clearly correlated with the E. coli dose 1 h after stimulation. Also the decay rate of those mRNAs reflected the pathogen load. The higher the concentration of E. coli, the faster and stronger was the up regulation and also the subsequent degradation of those particular mRNA species. Modulation of the mRNA concentration of tristetraprolin, a factor crucially involved in the mRNA degradation, followed the same pattern. In contrast, extent and kinetics of increasing the mRNA concentrations of serum amyloid A3 and lingual antimicrobial peptide were almost independent of the pathogen dose. We show that MEC perceive the information about the different pathogen concentrations and convert this signal into a calibrated synthesis of pro-inflammatory cytokines. We suggest that selective degradation of the mRNA molecules encoding those inflammatory cytokines contributes significantly to prevent an overshooting immune response in the udder.