Immune Imaging

Group Head: Professor Wolfgang Weninger

The Immune Imaging Group focuses on the visualisation of white blood cell (leukocyte) migration and interactions in real time within living tissues. Leukocytes are responsible for the recognition and destruction of invading microbes, such as viruses, bacteria and parasites, as well as tumour cells. Thus, it is important to understand the cellular and molecular mechanisms that regulate their trafficking through the body and their communication with host cells and pathogens.

The principle approach the group uses is a newly-developed imaging technique called two-photon microscopy. The cutting-edge technology allows for visualisation of fluorescently-tagged cells and molecules within the context of living tissues. This enables studying the dynamics of cell movements at a level of resolution that has not been reached before. Using this approach, the laboratory is investigating fundamental questions related to immune responses against infectious agents and tumours. It is hoped that a better understanding of these processes will, in the future, lead to improved vaccines and immuno-therapeutic strategies against disease.

We would like to unravel immunoregulatory mechanisms in infectious diseases and cancer by directly looking inside tissues as to how cells interact with their environment. Using a novel imaging technology, two-photon microscopy, we will be able to track cells in living tissues in real time. This will enable us to study how microbes and tumour cells are detected by leukocytes within living tissues. Together, these studies will shed completely new light on disease processes. This information may then be used to develop better vaccines, for example against influenza viruses, or immuno-therapies against cancer.

Research focus

Interplay of innate and adaptive immune cells during influenza virus infection
Influenza is an acute febrile respiratory illness caused by influenza virus infection and may trigger potentially life-threatening complications especially in the young and elderly. Immunity against influenza virus involves integration of the innate and adaptive immune system. However, we currently have a poor understanding as to how the interactions between the cellular components of the anti-influenza immune response are orchestrated in space and time. We will make use of intravital two-photon microscopy (2PM) to study how innate immune cell subsets, i.e. myeloid and plasmacytoid dendritic cells, induce the activation of antigen specific T cells in the lung draining lymph nodes during infection. In-depth insight into this process is not only important for increasing our knowledge of regulatory pathways of anti-viral immunity, but may, in the long-term, lead to the development of improved vaccine strategies against this important disease. This project is in collaboration with Dr Andrew Caton (Wistar Institute, Philadelphia, US) and Dr Stephen Turner (the University of Melbourne).

Mechanisms of T cell migration and interactions in tumours
Tumour cell-host cell interactions are critical determinants for the progression of neoplasms. Of particular importance are cytotoxic T cells, as they may recognise and destroy tumour cells. How T cells navigate within the tumour microenvironment, how they interact with neoplastic cells, as well as their overall contribution to the tumour micromilieu is not well understood. The project's long-term goal is to define the cellular and molecular cues responsible for the guidance of tumour infiltrating T cells (TIL) through the tumour stroma and mediation of their communication with neoplastic cells. We hypothesise that the quality of TIL migration and interactions with target cells determines whether a tumour is destroyed or grows unimpeded. To test our hypothesis, we will employ 2PM in our recently-developed subcutaneous tumour model. Our experiments will provide mechanistic insights into the events leading to tumour cell destruction or tumour immune evasion. Therefore, these studies have important implications for the optimisation of immuno-therapeutic strategies that aim to target cancer. This project is in collaboration with Dr Steve Reiner (University of Pennsylvania, Philadelphia, US) and Dr Sarah Russell (Peter MacCallum Cancer Centre, Melbourne).