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Doctoral thesis, 2018

Inflammatory mechanisms in bacterial infections: focus on mast cells and mastitis

Johnzon, Carl-Fredrik

Abstract

Inflammation is an unspecific response of the immune system to pathogens, for example, invasion by bacteria. This thesis focuses on two aspects of inflammation in the context of bacterial infections: (1) mast cells and (2) mastitis. Mast cells are potent proinflammatory leucocytes that have been implicated in the defence against bacterial infections. Mastitis is an inflammation of the mammary tissue and is one of the most economically destructive disease in the dairy industry worldwide. Here, mast cell synthesis of the potent pro-angiogenic vascular endothelial growth factor (VEGF) in response to stimuli with Staphylococcus aureus (S. aureus) was studied using an in vitro model of primary mouse mast cells. VEGF synthesis was found to be dependent on the presence of live whole bacteria. Previous in vivo investigations of the roles of mast cells in bacterial infections have been conducted using c-Kit-dependent mast cell-deficient mice. These mice suffer from numerous abnormalities in addition to the lack of mast cells. Instead, we used newer, cKit-independent mast cell-deficient mice (Mcpt5-Cre), which have fewer non-mast cell related abnormalities. We found no impact of the mast cell deficiency on the course of intraperitoneal S. aureus infection (e.g., bacterial clearance and cytokine production). We differentiated the virulence of, and response to, a set of clinical bacterial strains of bovine mastitis origin. Escherichia coli (E. coli) and S. aureus strains were injected intraperitoneally into mice. One E. coli strain(strain 127) was found to consistently cause more severe infection (judged by a clinical score) and induce a distinct profile of cytokines (CXCL1, G-CSF, CCL2). The concentrations of these cytokines correlated with both the clinical score and bacterial burden. The kinetics of the clinical and molecular changes that occurred during acute bovine mastitis were studied using a bovine in vivo model in which mastitis was induced by an intramammary infusion of E. coli lipopolysaccharide. Changes in clinical parameters (clinical score, milk changes, rectal temperature) as well as in milk and plasma cytokine concentrations and changes in the metabolome were registered. The progression of these changes occurred in the following order: (1) signs of inflammation in the udder and an increase in milk cytokine concentrations (after/at two hours), (2) visible changes in the milk and an increase in milk somatic cell counts (SCCs) (four hours), (3) changes in the plasma metabolome(four hours) and (4) changes in the milk metabolome (24 hours).

Keywords

mast cell, mastitis, inflammation, vascular endothelial growth factor

Published in

Acta Universitatis Agriculturae Sueciae
2018, number: 2018:19
ISBN: 978-91-7760-178-4, eISBN: 978-91-7760-179-1
Publisher: Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences

Authors' information

Johnzon, Carl-Fredrik
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)

UKÄ Subject classification

Cell and Molecular Biology
Immunology in the medical area
Other Veterinary Science

URI (permanent link to this page)

https://res.slu.se/id/publ/104196