The presence and function of Regulatory T and Th17 cells in cellular immunity in adenoids, tonsils and blood of Otitis Media-prone children

In chronic cases of otitis media, children will often require surgery to remove their adenoids and tonsils for two reasons; to remove the tissue source that provides a microbial reservoir that contributes greatly to infections, and to remove the inflamed tissue that causes unwanted pain and discomfort. As adenoids and tonsils are the local secondary lymph organs generating immune responses in upper respiratory infections, it is important to understand how they contribute to infections such as otitis media. Often when these secondary lymph structures are removed an improvement in disease outcome is observed without a known mechanism. Regulatory T cells (Tregs) are a subset of helper T cells that work in balancing the immune response to self and infection. Tregs exert a suppressive effect on local inflammatory responses to avoid unwanted tissue damage associated with a severe prolonged inflammatory response. Adenoids and tonsils are also a rich source of Tregs and how these cells and their counterpart, TH17 cells (pro-inflammatory) influence the development of otitis media is unknown. The findings of this project will provide the first insights into why the removal of the tonsillar tissue benefits the disease outcome of otitis media, and how Tregs and TH17 cells are contributing to the disease state of upper respiratory infections.

A novel strategy targeting quorum sensing molecules and catalase function to block Pseudomonas aeruginosa lung infection

Persistent lung infections resulting from Pseudomonas aeruginosa colonising the lungs are the major cause of morbidity and mortality in cystic fibrosis patients and in those with burns neutropenia or otherwise compromised immunity. P. aeruginosa is notoriously difficult to eradicate even with long-term antibiotic therapy, and there is evidence that the ability of the organism to form biofilms contributes to this resistance. Biofilm formation is controlled by small quorum sensing signal molecules (QSSMs), including a number of different acyl homoserine lactones (AHLs), the most frequently produced of which are N-3-(oxododecanoyl)-L-homoserine lactone (OdDHL) and butyryl L-homoserine lactone (BHL). It has been widely postulated that blocking quorum sensing and biofilm formation could have therapeutic benefit. In particular, it has been speculated that blocking of QSSM actions could be beneficial by limiting the ability of P. aeruginosa to form biofilms and thus to express a range of quorum-sensing dependent virulence factors.Another component associated with the ability to avoid host defences is catalase A through decomposing hydrogen peroxide released from phagocytes.

Assessment of bacterial adherence onto respiratory epithelia

The human respiratory tract is colonised by multiple bacterial species at any given time and bacterial adherence to mucosal and epithelial surfaces is an important step in its colonisation. Various bacterial adhesions facilitate localisation of bacteria by different receptor molecules present on epithelial cells. In a polymicrobial environment, it is important to understand the extent and mechanisms by which different bacteria interact with each other and the host to cause disease. This project is investigating how different bacteria may interact or compete with each other when colonising the host and alter their ability to adhere and contribute to various respiratory infections, including otitis media.

Invitro modelling of host-microbe dynamics involved in biofilm formation by Streptococcus pneumoniae and non-typeable Haemophilus influenzae

Otitis media or middle ear infection is a common pediatric disease with significant impact on financial outcomes for both families with children as well as on the health system worldwide. The concept of bacterial biofilms in otitis media is well known. This project is investigating the ability of co-existing bacteria to form biofilm following adherence to respiratory cells. This will provide information on how biofilms promote persistent infections by altering the ability of bacteria to produce biofilm in a polybacterial environment. The findings will contribute to develop better therapeutic approaches towards respiratory infections.

Research is supported by NHMRC and CQUniversity competitive grants.