Immune responses to pathogenic bacteria
Bacterial infectious diseases account for ~10 x 106 deaths annually. Our research is directed toward maximising the chances of developing more effective vaccines and antimicrobial drugs through a better understanding of how the immune system combats bacterial infections.
Immune responses in infected tissues are essential for controlling invading pathogens in the early phases of infection. Despite having a vital role, the main cells and factors that control innate immune responses in tissues are poorly defined. To gain an integrated understanding of the in vivo innate immune network in lung tissue, we are investigating the immune response to the intracellular lung bacterial pathogen Legionella pneumophila. This important opportunistic pathogen causes Legionnaires’ disease, a vastly under diagnosed disease that is associated with high rates of morbidity and mortality.
We have revealed a cooperative circuit in the response to Legionella infection. Inflammatory dendritic cells induced production of the important cytokine IFNγ by lymphoid. IFNγ, in turn, was necessary for bacterial killing by the inflammatory dendritic cells. Surprisingly, macrophages that engulf bacteria did not respond to IFNγ.
We will continue this project by addressing a number of important questions each of which could be the basis of a research student’s project.
- Why are macrophages unable to kill bacteria even in the presence of stimulatory cytokines like IFNγ?
- We have discovered that another cytokine IL23 plays an important role in combatting Legionella.
Which cells make IL23 and how does it act to kill bacteria?
- Macrophages are the cell type inside which Legionella bacteria replicate. Why can’t Legionella replicate in other similar cells like dendritic cells?
- IFNγ can convert inflammatory dendritic cells into bacterial killers. What are the key molecular changes that are induced by IFNγ?
Techniques commonly used in this laboratory:
Flow cytometry, cell culture, use of mice and infection of mice, immunoblotting, immunolocalisation in cells, quantitative PCR, bioinformatic analysis of expression data.
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