Variation in fibroblast expression of toll-like receptor 4 and lipopolysaccharide-induced cytokine production between animals predicts control of bacterial growth but not severity of Escherichia coli mastitis

Abstract

Mastitis caused by environmental pathogens such as Escherichia coli is highly problematic to the dairy industry because it incurs substantial cost and tends to be difficult to manage. An effective innate immune response by the host is key to controlling infection, but it should also limit collateral damage to the mammary gland. Between-animal differences in mastitis severity have been attributed to variability in the innate response. In the current study, we used primary dermal fibroblast as a model to rank animals based on composite expression of the toll-like receptor 4 gene (TLR4) and lipopolysaccharide (LPS)-induced IL-8 and IL-6 protein production. Animals ranked as high and low responders (HR and LR, respectively) were then infected with the P4 strain of E. coli to determine how difference in rank would affect response to mastitis. All animals developed an acute response to the infection with varying degrees in severity; however, HR animals had an elevated somatic cell count and fever response at 12 h post-infection and greater production of milk IL-8 at 24 h post-infection. The HR animals were also significantly more capable of limiting bacterial growth. No differences in post-infection milk production or concentrations of milk BSA were measured. The current study indicates that HR animals have an early upregulation in their innate response that is beneficial for bacterial clearance; however, they are equally susceptible to tissue damage caused by an exuberant response to the infection. The dermal fibroblast may be used in conjunction with other cell types to determine how the innate response is regulated to mitigate unnecessary injury to the mammary gland while still effectively clearing the pathogen.

Meloxicam affects the inflammatory responses of bovine mammary epithelial cells

“…On the other hand, the role of leukocytes as first line responders is important, and maintenance of a certain level of neutrophil infiltration is essential for the phagocytosis and elimination of bacteria from the mammary gland to cure mastitis (Aitken et al, 2011). Therefore, chemoattractants are of importance for the mammary immune response, and Korkmaz et al (2018) found that cows with greater production of milk IL-8 were more capable of limiting bacterial growth during mastitis than cows with lower milk IL-8.…”

Lactobacillus johnsonii L531 Ameliorates Escherichia coli-Induced Cell Damage via Inhibiting NLRP3 Inflammasome Activity and Promoting ATG5/ATG16L1-Mediated Autophagy in Porcine Mammary Epithelial Cells

“…For instance, TLR2 identifies cell wall components of gram-positive bacteria [ 40 , 41 ], whereas TLR4 identifies LPS from gram-negative bacteria [ 16 , 42 ]. Studies show that TLR4 is the main pattern recognition receptor in response to E. coli -induced mastitis in mice, goats and dairy cows [ 43 , 44 , 45 ]. We found that E. coli –induced an up-regulation of Tlr4 in PMECs at 6 h after E. coli infection.…”

Three Novel Players: PTK2B, SYK, and TNFRSF21 Were Identified to Be Involved in the Regulation of Bovine Mastitis Susceptibility via GWAS and Post-transcriptional Analysis

“…In the production process, mastitis is still not fully controlled despite thorough hygiene, antibiotic treatment, vaccination, and other measures (52). Therefore, the association between dairy cows' genetic variation and mastitis is receiving more and more attention (18, 35, 53, 54). This study sought to screen for significant differential SNPs associated with clinical mastitis via GWAS-2bRADseq, to identify potential clinical mastitis susceptibility or resistance genes and to verify for their authenticity and role in mastitis resistance/tolerance in vitro and in vivo .…”