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Infection and Immunity, June 2008, p. 2802-2807, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00051-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

β-Hydroxybutyrate Abrogates Formation of Bovine Neutrophil Extracellular Traps and Bactericidal Activity against Mammary Pathogenic Escherichia coli{triangledown}

Navit Grinberg,1 Sharon Elazar,1 Ilan Rosenshine,2 and Nahum Y. Shpigel1*

The Koret School of Veterinary Medicine, Faculty of Agriculture, The Hebrew University of Jerusalem, POB 12, Rehovot 76100, Israel,1 Molecular Genetics and Biotechnology, Faculty of Medicine, the Hebrew University of Jerusalem, POB 12272, Jerusalem 91120, Israel2

Received 15 January 2008/ Returned for modification 11 February 2008/ Accepted 3 April 2008

Escherichia coli is an important bacterial species isolated from bovine mastitis. The rate of neutrophil recruitment into the mammary gland and their bactericidal activity largely affect the severity and outcome of the disease. Ketosis is a common metabolic disease, and affected dairy cows are known to have increased risk for mastitis and other infectious conditions. The disease is associated with high blood and milk levels of β-hydroxybutyrate (BHBA), previously shown to negatively affect neutrophil function by unknown mechanisms. We show here that the mammary pathogenic E. coli strain P4 activates normal bovine neutrophils to form neutrophil extracellular traps (NETs), which are highly bactericidal against this organism. Preincubation of these neutrophils with increasing concentrations (0.1 to 8 mmol/liter) of BHBA caused a fivefold decrease of E. coli P4 phagocytosis, though intracellular killing was unaffected. Furthermore, BHBA caused a 10-fold decrease in the NETs formed by E. coli P4-activated neutrophils and a similar decrease in NET bactericidal activity against this organism. These negative effects of BHBA on bovine neutrophils might explain the increased susceptibility of ketotic cows to mastitis and other infectious conditions.

* Corresponding author. Mailing address: The Koret School of Veterinary Medicine, POB 12, Rehovot 76100, Israel. Phone: 972 8 9489534. Fax: 972 8 9489138. E-mail: shpigeln{at}agri.huji.ac.il

{triangledown} Published ahead of print on 14 April 2008.

Editor: B. A. McCormick

Infection and Immunity, June 2008, p. 2802-2807, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00051-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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