Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells.
Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC) challenged with the mastitis pathogen Escherichia coli (E. coli). Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from milk and challenged in culture with 3 mM BHBA and E. coli. pbMEC stimulated with E. coli for 6 h or 30 h showed an up-regulation of several innate immune genes, whereas co-stimulation of pbMEC with 3 mM BHBA and E. coli resulted in the down-regulation of CCL2, SAA3, LF and C3 gene expression compared to the challenge with solely the bacterial stimulus. These results indicated that increased BHBA concentrations may be partially responsible for the higher mastitis susceptibility of dairy cows in early lactation. Elevated levels of BHBA in blood and milk during negative energy balance and ketosis are likely to impair innate immune function in the bovine mammary gland by attenuating the expression of a broad range of innate immune genes.
Chair of Animal Physiology and Immunology, Technische Universität München, Freising, Germany.
Maria
http://orcid.org/0000-0001-6719-7539
M
Hillreiner
Chair of Animal Physiology and Immunology, Technische Universität München, Freising, Germany.
Claudia
C
Flinspach
Chair of Animal Physiology and Immunology, Technische Universität München, Freising, Germany.
Michael W
MW
Pfaffl
Chair of Animal Physiology and Immunology, Technische Universität München, Freising, Germany.
Heike
H
Kliem
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D003176:Complement C3 / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D004926:Escherichia coli / Q000254:growth & development*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007781:Lactoferrin / Q000235:genetics / Q000276:immunology; D008321:Mammary Glands, Animal / Q000276:immunology / Q000382:microbiology; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics* / Q000276:immunology
D018932:Chemokine CCL2; D003176:Complement C3; D000685:Serum Amyloid A Protein; D051193:Toll-Like Receptors; D007781:Lactoferrin; D020155:3-Hydroxybutyric Acid