Host-pathogen interaction using the whole blood models

In order to investigate the complex interactions between the immune cells and pathogens, the aim of this thesis was to establish an ex vivo whole-blood model using murine and avian blood and to investigate how the model pathogens Candida albicans, Escherichia coli, Staphylococcus aureus, Salmonella Enteritidis and Salmonella Gallinarum interact with various host components in this environment. In the first part of our study, the established whole-blood model was used to understand the immune responses in the peripheral blood of two chicken lines differing in egg-laying performance to infection with either C. albicans, S. aureus, or E. coli. Our results demonstrated chicken-line and pathogen-dependent differences in pathogen survival, immune cells viability, and their interactions with the pathogens. Comparing different avian leukocyte subsets, the bacterial pathogens were found to be most associated with monocytes followed by the granulocytes. In contrast, C. albicans more frequently interacted with granulocytes and at a lower rate with monocytes. C. albicans was observed to have stronger impact on immune cell viability in chicken than to the bacterial species. These studies were furthermore extended to Salmonella enterica sp., which are important and widely studied pathogens in chickens. The second part of the study provided insights into interactions between murine blood and C. albicans, E. coli and S. aureus. Our results indicated relatively low pathogen clearance and pathogen-dependent differences regarding rates of association with immune cells. Using a filament deficient C. albicans mutant it was shown that increased filamentation does not explain the reduced killing. Likewise, the lower absolute number of neutrophils in murine blood could not fully explain higher fungal survival. Lack of prior exposure to pathogens and absence of adaptive responses, such as antibodies, appear to contribute to low pathogen clearance.


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