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Delineating the Immune Mechanisms Required by Murine Neutrophils and Macrophages for Clearance of Burkholderia pseudomallei, the Causative Agent of Melioidosis
Contents
Abstract
Acknowledgments
Contents
List of Figures
1 Literature Review
1.1 Burkholderia pseudomallei (Bp)
1.2 Bp pathogenesis and virulence factors
1.3 Interaction of host immune system with Bp
1.4 Macrophages and Bp infection
1.5 Neutrophils and Bp infection
1.6 Macrophages and neutrophils
1.7 Why is it important to study Bp?
1.8 Goal and significance of our studies
2 Materials and Methods
2.1 Bacterial strains and culture
2.2 Mice
2.3 Antibiotic sensitivity assays
2.4 Cell isolation and culture
2.5 Bacterial opsonization
2.6 Complement deposition analysis
2.7 Complement-mediated direct killing of bacteria
2.8 Intracellular growth of bacteria
2.9 Quantification of neutrophil respiratory burst
2.10 Statistical analyses
3 Results and Findings
3.1 Kanamycin sensitivity of Bp and Bt
3.2 Can primary murine macrophages inherently clear Bp, Bt or the acapsular mutant?
3.3 Can primary murine neutrophils inherently clear Bp, Bt or the acapsular mutant?
3.4 How do Burkholderia spp interact with serum opsonins?
3.5 What is the effect of serum opsonization on uptake and persistence of Bp, Bt and the acapsular mutant by murine macrophages?
3.6 What is the effect of serum opsonization on persistence of Bp, Bt and the acapsular mutant in murine neutrophils?
3.7 Does serum opsonization of Burkholderia spp. lead to ROS production by murine neutrophils?
3.8 What is the effect of specific antibody and serum opsonization on Burkholderia spp. persistence in phagocytes?
3.9 What pre-activation do murine macrophages require to clear Bp and Bt?
4 Discussion
4.1 Macrophages and neutrophils are inherently unable to clear Bp, the acapsular mutant and Bt
4.2 Burkholderia strains show differences in complement deposition but are equally resistant to complement-mediated direct killing
4.3 Macrophage responses to Bp suggesting the importance of Th1 type response in Bp clearance
4.4 Neutrophils are efficient at killing Bp once opsonized with sufficient concentration of serum by rapid ROS production
4.5 Specific antibodies help increase complement deposition on Bp but do not help in enhancing either bacterial uptake or clearance by macrophages or neutrophils in presence of complement
4.6 Role of Bp capsule as a virulence factor and potential reasons for differences in virulence between Bp and Bt in vivo
4.7 Significance and future studies
ReferencesBài viết liên quan
