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Title: Response to intramammary challenge with putatively host-adapted and non-adapted strains of Streptococcus uberis in cattle
Author: Tassi, Riccardo
ISNI:       0000 0004 5916 5280
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2015
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Streptococcus uberis is an important cause of intramammary infection in dairy cattle. Strains of S. uberis appear to differ in their ability to cause disease based on previous epidemiological studies. We explored the pathogenicity of 2 strains of S. uberis, where one strain represented a putatively host-adapted type based on its ability to cause persistent infection and to spread from cow to cow in a lactating herd. This type was part of a clonal complex that is commonly associated with bovine mastitis. The other strain, which was isolated from a transient infection in a single animal in the same herd and did not belong to any known clonal complex, was selected as putatively non-adapted type. Cows (6 per strain) were experimentally challenged in a single hind quarter and the adjacent hind quarter was used as mock challenged control quarter. Both strains showed an equal ability grow in milk of challenge animals in vitro. All cows that were challenged with the putatively host-adapted strain developed clinical signs of mastitis, including fever and milk yield depression as well as elevated somatic cell count due to influx of polymorphonuclear leucocytes and lymphocytes. The cytokine response followed a specific order, with an increase in IL-1β, IL-6 and IL-8 levels at the time of first SCC elevation, followed by an increase in IL-10, IL-12p40 and TNF-α levels approximately 6 h later. In 4 of 6 animals, IL-17A was detected in milk between 57 and 168 h post challenge. The increase in IL-17A levels coincided with inversion of the pre-challenge CD4+:CD8+ T lymphocyte ratio, and was observed from 96 h post challenge. This was followed by normalisation of the CD4+:CD8+ ratio due to continued increase of the CD8+ concentration up to 312 h post challenge. Spontaneous resolution of infection was observed in 5 animals and coincided with a measurable IL-17A response in 4 animals, suggesting that IL-17 may be involved in the resolution of intramammary infection. To explore the mechanism of action of IL-17A we stimulated bovine PMN and bovine blood derived macrophages with recombinant IL-17A in vitro. IL-17A enhanced the killing ability of phagocyte toward the challenge strain. With the exception of minor elevation of IL-8 levels, no clinical, cytological or immunological response was detected in quarters challenged with the non-adapted strain. The observed strain specific pathogenicity was consistent across animals, implying that it is determined by pathogen factors rather than host factors. We further studied in vitro possible mechanisms involved in the differences observed between the two strains such as ability to adhere to the mammary epithelial cells, ability to resist to killing by phagocytes and ability to form biofilm. The adapted strain FSL Z1-048 showed an increased ability to adhere to the epithelial cells and an increase ability to resist to killing of monocyte derived macrophages. These mechanisms thus could potentially explain the in vivo observations.
Supervisor: Zadoks, Ruth ; McNeilly, Tom Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: cattle ; mastitis ; interleukin-17A ; Streptococcus uberis ; lymphocyte