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Intravital Microscopy in Infection and Immunity (Group A.Müller)

General introduction

Whether or not an infected organism is successful in defending itself against a pathogen depends primarily upon the interaction of the cells within the immune system - both among one another and with the pathogen. The “language” of these interactions, soluble and membrane-linked signal molecules, has been thoroughly examined in recent years. The manner in which these signals are exchanged within the living organism is still unclear. With the aid of specialized microscopy technologies, the interplay between host and pathogen can be tracked nowadays in living tissues.

Movie: Intravital 2-photon movie of CD4+ T cells (blue) interacting with the intracellular parasite Leishmania major (yellow) in the infected skin: Leishmania-infected cells carry parasite antigen on their surface, effector T cells specific for this antigen stop their movement through the tissue upon encountering infected cells and start secreting cytokines. This instructs the infected cells to launch intracellular defense mechanisms. A 90 minutes time period is shown in the movie. Close interactions between T cells and parasite-infected cells are indicated in white.

Our research:

When pathogens infect an organism, our immune system generally initiates defenses to combat the intruder. Whether this is successful depends primarily on the interaction of the cells of the immune system with each other and with the pathogen. New developments in microscopy have made it possible to track the behaviour of immune cells in the tissue. This permits studying in real time which interactions are necessary for protective immunity.

This has greatly contributied to our understanding of how the immune response is initiated, continued and - when necessary - switched off again. All of these processes are critical in order to defend the organism from pathogens and prevent the initiation of injurious auto-immune diseases.

Our research group “Intravital Microscopy in Infection and Immunity” (INMI) has specialized in so-called “multi-photon microscopy”, a technique that permits tracking the interaction between host and pathogen within living tissue. Our research focuses on the issue of how a pathogen reacts to the stress imposed by immune response. By using pathogens with fluorescent reporter systems (pathogen-produced dyes that react to biological changes), we can track processes such as cell division, protein production as well as the activity of stress-induced enzymes in living pathogens.

From measuring these parameters during the infection we can yield insights into when and under what conditions the immune response is most effective. Since the changes in pathogen biology can also influence their sensitivity to antibiotics, we can also find out how the immune response can best be supported with therapeutic measures.

Andreas Müller:

“We are trying to find out how a pathogen reacts to stress that it is exposed to during the immune response.”

Andreas Müller received his doctorate at the ETH Zurich, where he studied the early stages of Salmonella infection at the Institute for Microbiology in the working group of Wolf-Dietrich Hardt.  He then continued with research residences at the Institut Pasteur in Paris in the working group for Immune Dynamics of Philippe Bousso with studies on the signal range of active T-cells in tissue, and at the University of Lausanne in the Laboratory for Pathology of Leishmania Infections of Fabienne Tacchini-Cottier, where he analyzed the influence of granulocytes in the immune response against Leishmania. Andreas Müller has been appointed Director of the research group “Intra-vital microscopy of infection and immunity” in December of 2013.