4 minute read
“Microscopy has undergone a revolution over the past 20 years”
Prof Dr Matthias Gunzer receives many e-mails every day. They are part of everyday life for the head of the Department of Biospectroscopy at ISAS and director of the Institute for Experimental Immunology and Imaging /Imaging Centre at the Essen University Hospital. But in February 2021, his mailbox had a surprise in store for him – an invitation for a review from a special addressee. The immunologist explains in an interview how this came about in the first place and what ultimately became of it.
How did you come to be invited to the review?
Prof Dr Matthias Gunzer heads the department of Biospectroscopy at ISAS and is Director of the Institute for Experimental Immunology and Imaging/Imaging Centre at Essen University hospital.
Gunzer: The invitation from Dr Ronald Germain of the National Institute of Allergy and Infectious Diseases (NIAID) in the USA came by e-mail and was completely unexpected for me. It is an honour to be asked for an opinion by such a well-known researcher. And Immunological Reviews is a renowned journal. That’s why my decision was a foregone conclusion from the very first. I also had some ideas in mind from the beginning and knew that I would like to collaborate on the review with Prof Dr Anika Grüneboom, who heads the Bioimaging research group in my department here at ISAS. We then agreed that it would be nice to involve our doctoral students in the review as well, so we divided the tasks amongst ourselves and regularly exchanged updates and came up with some exciting ideas and food for thought in the process. In the end, I think we were all able to learn something new whilst working for the review.
In your paper, you focus on the analysis of neutrophils and macrophages in sterile and infectious inflammation using imaging. What conclusions have you come to, or what is »state of the art« in this respect?
Gunzer: Around 150 years ago, physician Rudolf Virchow discovered that the cells of the immune system can move. We’ve come an incredibly long way since then. In the review, for example, we focused on recent findings in confocal microscopy and intravital two-photon microscopy. In combination with modern mouse models, such as the »catchup mouse« we developed, these methods contribute significantly to a better understanding of the innate immune response. Because intravital microscopy is excellent for observing individual cells, research has been able to break down exactly how and why neutrophils (► p. 70) and macrophages move. We can also measure and quantify them reliably. However, when it comes to examining larger areas, this
Grüneboom A, Aust O, Cibir Z, Weber F, Hermann DM & Gunzer M Imaging innate immunity Immunological Reviews, 2022; 306:293–303
https://doi.org/10.1111/imr.13048
method quickly reaches its limits. Therefore, imaging at the tissue level or »mesoscopic level« using light sheet fluorescence microscopy is required in order to fully understand innate immunity. This covers the range from one micrometre to several centimetres. It also makes light sheet fluorescence microscopy an essential tool in modern microscopy.
What is the future of imaging in terms of innate immune response?
Gunzer: When the development of the light microscope reached its technically feasible limit a few years ago, many people thought that research in this field had come to an end. Fortunately, a revolution has occurred in microscopy over the past 20 years with innovations that we once could barely have imagined, and so it is difficult for me to predict what technical possibilities the future may hold. However, there are two things that are of burning interest to me – one is to be able to observe the movement of neutrophils and macrophages in living humans. This type of microscopy, known as »intravital microscopy«, is already possible in smaller mammals, and from this, we’ve already learned that neutrophils increasingly migrate into tumours. Second,
INFECTIOUS & STERILE INFLAMMATION
Every inflammation is the reaction of the body's own defence system, the immune system, to a stimulus. This can have various causes. Often pathogens like bacteria or viruses are responsible for the inflammation. But foreign elements, such as splinters, mechanical stimuli or a vascular blockage, as in a heart attack or stroke, can also cause an inflammatory reaction. Experts call the latter scenario sterile or aseptic inflammation, because no pathogens are involved in its development. One example for sterile infections is rheumatoid arthritis.
the question remains as to what we do with this newly gained knowledge. We do not yet have any use for it; at least, I’m not aware of any diagnostic method that examines the movement of these cells as a parameter. It also remains to be seen what happens if the neutrophils are prevented from moving, so there are still plenty of questions for the next years and decades (laughs). One thing is certain however – as long as biomedical research exists, scientists will continue to study the movement of immune cells.
(The interview was conducted by CMP.)
