Seminar: Host-pathogen interactions: Exploring Bordetella LPS signalling and a humanized mouse model of infection

Abstract: Bordetella pertussis, a Gram-negative coccobacillus, is the causative agent of whooping cough which is resurging worldwide in 2024. Bordetella LPS, upon TLR4 recognition, signals via either the MyD88 or the TRIF pathway. While the first is associated with strong proinflammatory responses, the latter is linked to DC maturation and T cell priming. My study investigates the influence of certain structural features of Bordetella LPS on these pathways, i.e the O antigen, the number of acyl chains in LPS and the glucosamine modification of the lipid A backbone phosphates. This knowledge not only furthers our understanding of LPS features that influence TLR4 downstream signalling, but also aids in engineering LPS to modulate consequent immune responses and thus inform vaccine design.

In parallel, I will also be assessing the feasibility of using the humanized PBMC mouse model for the study of B. pertussis infection as the ideal model, the baboon model, is inaccessible, and the more commonly used mouse model responds to infection differently compared to humans.