Host response to polymicrobial infections in the lung

  • Yuan Ji

Student thesis: Doctoral ThesisPhD


The aims of this thesis were to investigate the differences in host responses to mono- and co-infection by common pulmonary pathogens Staphylococcus aureus and Burkholderia cepacia complex, to interpret the host receptor and signalling cascades targeted by S. aureus, and to characterise S. aureus immunomodulatory factors. Disruption of the intact airway epithelial barrier and cellular internalisation were observed with both species. B. cenocepacia J2315 activated TLR-mediated MAPK and NF-κB signalling pathways, subsequently eliciting a robust interleukin (IL)-8 production. However, when airway epithelial cells were co-treated with B. cenocepacia live bacteria and S. aureus supernatants, the pro-inflammatory response was subverted by Staphylococcal effectors. This anti-inflammatory effect was widely exhibited in S. aureus isolates tested, and was mediated via TLRs but not via the IL-1 receptor or the tumour necrosis factor receptor. TLR4 but not TLR5 was partially blocked by S. aureus secreted products, though the TLR4 agonist lipopolysaccharide did not affect IL-8 expression at a high concentration. The Staphylococcal effectors were preliminarily characterised as small, heat-stable, non- proteinaceous, and not cell wall-related factors.
This thesis demonstrates the complex nature of host response in a co-infection model and provides insight into a novel S. aureus immune evasion mechanism, as well as a therapeutic intervention of abnormal chronic inflammation.
Date of Award13 Feb 2019
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorMalcolm L Watson (Supervisor) & Albert Bolhuis (Supervisor)

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