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

Johnzon, Carl-Fredrik (2018). Inflammatory mechanisms in bacterial infections: focus on mast cells and mastitis. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., 2018:19, 1652-6880
ISBN 978-91-7760-178-4
eISBN 978-91-7760-179-1
[Doctoral thesis]

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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).

Authors/Creators:Johnzon, Carl-Fredrik
Title:Inflammatory mechanisms in bacterial infections: focus on mast cells and mastitis
Series/Journal:Acta Universitatis agriculturae Sueciae
Year of publishing :2018
Number of Pages:79
Papers/manuscripts:
NumberReferences
IJohnzon, CF., Rönnberg, E., Guss, B., Pejler, G*. (2016). Live Staphylococcus aureus induces expression and release of vascular endothelial growth factor in terminally differentiated mouse mast cells. Frontiers in Immunology, DOI: 10.3389/fimmu.2016.00247.
IIRönnberg, E*., Johnzon, CF., Calounova, G., Garcia Faroldi, G., Grujic, M., Hartmann, K., Roers, A., Guss, B., Lundequist, A., Pejler, G. (2014). Mast cells are activated by Staphylococcus aureus in vitro but do not influence the outcome of intraperitoneal S. aureus infection in vivo. Immunology, 143 (2), 155 – 163.
IIIJohnzon, CF., Artursson, K., Söderlund, R., Guss, B., Rönnberg, E., Pejler, G*. (2016). Mastitis pathogens with high virulence in a mouse model produce a distinct cytokine profile in vivo. Frontiers in Immunology, DOI: 10.3389/fimmu.2016.00368.
IVJohnzon, CF*., Dahlberg, J., Gustafson, AM., Waern, I., Moazzami, AA., Östensson, K., Pejler, G*. The effect of lipopolysaccharide-induced experimental bovine mastitis on clinical parameters, inflammatory markers and the metabolome: a kinetic approach. (Manuscript) Paper
Place of Publication:Uppsala
Publisher:Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-7760-178-4
ISBN for electronic version:978-91-7760-179-1
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Cell and Molecular Biology
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Immunology in the medical area
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Other Veterinary Science
Agrovoc terms:mast cells, mastitis, inflamation, dairy cows
Keywords:mast cell, mastitis, inflammation, vascular endothelial growth factor
URN:NBN:urn:nbn:se:slu:epsilon-e-4883
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-4883
ID Code:15465
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: Carl-Fredrik Johnzon
Deposited On:16 May 2018 13:27
Metadata Last Modified:16 May 2018 13:27

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