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About our research interests

Our research centers on understanding the interaction of bacteria and the molecules they express, with the host's immune system. The complexity of these interactions is such that bacteria can promote pro- and anti-inflammatory immune responses in addition to evading the immune responses elicited to eradicate them. Our primary interest is the immune response elicited by the gram-positive bacterium Staphylococcus aureus.

The rates of infection with methicillin resistant (MRSA) strains of S. aureus are well documented. To facilitate any future success in the development of therapeutic alternatives to antibiotics e.g. immunomodulatory therapies and vaccines, a more lucid understanding of host-pathogen interactions must first be established. Despite major research efforts a robust S. aureus vaccine still eludes us, in part due to the undeniable fact that antibody mediated immunity does not appear sufficient to provide protection. It is clear that significant efforts must now be made to understand precisely the cellular immune response elicited upon exposure to this organism. An important point to note is that in contrast to its invasive infectious potential, S. aureus is regularly found as commensal coloniser of the skin and anterior nares. More than 50% of the adult population are colonised with S. aureus in their noses. Throughout life therefore, our immune system is continually exposed to this organism, in the non-infectious setting of nasal colonisation and also during infection which can be superficial or under certain circumstances severe and sometimes life threatening.

1. The role played by specific T-cell subsets during acute S. aureus infections.

During S. aureus infections specific sub-sets of T-cells becomes activated to produce particular cytokines that are required to co-ordinate an appropriate local neutrophil response that is vital for the successful clearance of infection. We have previously identified a novel mechanism by which a carbohydrate molecule expressed by S. aureus can directly activate CD4⁺ T-cells to produce the cytokine IFN-g and demonstrate that at the S. aureus infection site this IFN-g promoted CXC chemokine production and facilitated neutrophil recruitment. Currently we are investigating gdTCR⁺ T-cells as the primary source of the cytokine IL-17 during S.aureus surgical wound infection.

2. Understanding T-cell memory to S.aureus

A high proportion of the population are colonised with S.aureus in their noses and almost everyone has been exposed to sub-clinical infection with this organism. However we understand very little about how exposure to S.aureus throughout life can impact upon the host's immune response to subsequent invasive infection. We are currently investigating how exposure to S.aureus can modulate memory T-cell phenotype/function.

3. Immune evasion by S.aureus

Neutrophils represent the first line of defense against invasion by S. aureus and are a critical determinant in the outcome of infection. However, some studies suggest PMN may actually contribute to pathogenesis by harboring viable S. aureus intra-cellularly. We have recently demonstrated heightened PMN recruitment associated with increased pathogenesis during surgical wound infections and demonstrated that local administration of CXC chemokines actually facilitated survival of organisms within neutrophils isolated from the infection site. We are currently investigating the mechanism behind this effect. If neutrophils can act as reservoirs for viable organisms during infection with S. aureus, then any dysregulation in the neutrophil response could facilitate persistence of infection. Targeting the neutrophil to ensure an efficient neutrophil response may prevent bacteria from gaining a survival advantage over the host.

4. Investigating the immunomodulatory properties of a Streptococcus pneumoniae capsular polysaccharide.

These studies propose to define the mechanisms by which the commensal organism S. pneumoniae and the molecules it expresses can directly influence immune cell phenotypes. Serotype 1 strains of S. pneumoniae express a zwitterionic capsular polysaccharide (Sp1) . This molecule has been previously been shown to activate CD4⁺ CD45RB^low T-cells to produce IL-10. We are currently investigating the anti-inflammatory properties of this molecule for the treatment of inflammatory and allergic diseases.