Insights From Immunologists: Professor Hugh Perry

F4/80, clone CI:A3-1, is a well-characterized and extensively referenced macrophage and microglia marker. Recently, we had the honor of joining Professor Siamon Gordon, the father of F4/80, in celebrating its discovery over 40 years ago, alongside the past members of his lab who in the decades since have made significant contributions to macrophage research, and the scientific landscape as a whole.

We spoke to Professor Hugh Perry, who collaborated with Siamon to advance our understanding of macrophages in the brain. Hugh originally trained as a neuroscientist before becoming interested in the immune system and has since focused his work on the interface between neuroscience and immunology. He has contributed extensively to research in neuroinflammation and neurodegenerative disorders and currently works as a consultant to the UK Dementia Research Institute (UK DRI).

Bio-Rad (BR): When did you first become interested in a career in science?

Hugh Perry (HP): When I was at school in the 1960s, students were streamed into either science or arts, and the decision was really made by one’s teachers rather than by oneself. I was naturally curious, so I was happy to be in the science group.

At school, we had no idea how science was actually done. People thought that it was endless “eureka” moments. I think it’s only in recent years that scientists have made the effort to communicate with the public and help them understand what scientists actually do. I had no idea about what a career in science would be while I was at school. I went to the University of Oxford, and I did a degree in physiological sciences with the goal of becoming a medic. But my tutor at the time, John Stein, was very encouraging. He knew I was interested in neuroscience, and he persuaded me to consider research and a PhD.

I was fortunate enough to start a PhD with an eminent vision scientist, Alan Cowey, where I studied the retina, investigating which cells communicated with the brain and how. I was completely engrossed in the topic.

BR: How did you become specifically interested in macrophages?

HP: After I’d finished my PhD, I stayed at the University of Oxford to carry on the work on the retina and its connections to the brain. Vision research seemed to be the place to be in the 1980s. It was a very dynamic field and a lot was happening. One of the things we wanted to do was to study developmental processes in the retina to see how this population of cells that communicated with the brain, the retinal ganglion cells, emerged during development.

As with many other parts of the central nervous system, there’s a lot of cell death that occurs — supernumerary cells die by apoptosis and they’re cleared from the system. We saw these cells that looked suspiciously like macrophages in the developing retina. But this was in a simple cell stain and we wanted some way that we could label them to say yes indeed they are macrophages.

A colleague of mine suggested that I should go to the Sir William Dunn School of Pathology, where Professor Siamon Gordon had his laboratory. His laboratory was involved in looking at tissue macrophages using immunohistochemistry in many different organs of the mouse. And, of course, the one place they had not yet looked was the brain. Siamon was very generous and told me about the wonderful reagent they had, F4/80, which is a pan macrophage marker and would enable us to identify these cells as macrophages.

 In the mid-1980s, in collaboration with one of his postdocs, David Hume, we studied the postnatal development of macrophages in the brain, and they were indeed phagocytosing these apoptotic cells. But more interesting was that this antibody also labeled cells that are known as microglia, which we now know are the resident macrophages in the brain.

A postdoc with me, Linda Lawson, did a fantastic study looking at microglia throughout the brain, and quantified and documented the heterogeneity of this cell population. This was really our introduction to macrophages in the brain.

BR: Can you describe a highlight from your career?

HP: I think I’ve been lucky. I had some pretty interesting highlights in different areas but one finding that for me personally was very important in changing one’s thinking was an observation made with Siamon that CD4 was expressed on microglia in the brain.

In the late 1980s, HIV had just become a huge global problem and many of the people dying with HIV had severe cognitive problems. Somehow the virus was getting into the brain, replicating in the brain, and then causing considerable damage. We now know that this was due to the expression of CD4, which the virus uses for entry into microglia.

At the time, microglia were in the background of neuroscience. Now, microglia have come to the forefront of the field in many aspects of research, it has been really interesting to watch this area of science evolve over time.

BR: Can you tell us about your current research/role?

HP: I am a retired emeritus professor at the University of Southampton and I’m also a consultant to the UK Dementia Research Institute. I played a role in helping to establish the UK DRI. It has gone from virtually 0 to 800 plus people in seven different centers across the UK. It’s really doing fantastic, fundamental work across dementia research.

BR: What advice would you give to early career scientists?

HP: Many exciting new discoveries are being made at the interface between different fields. Who would have thought that neuroimmunology, the interface between neuroscience and immunology, would be such a dynamic area? However, it’s difficult to be an expert in both neuroscience and immunology, what you need are good colleagues and to have an open mind about how you find the right people to advise you in different areas.

There are also dramatic changes in technology and some of this is non-trivial. To be a master of all these different imaging technologies, sequencing technologies, bioinformatics, and so on is impossible no matter how excited and ambitious you are. It’s very difficult to go it alone. I would encourage young scientists to recognize that science is a collaborative process and seek collaborators to help them understand technology and different fields, as this is where the exciting new discoveries lie.

Thank you, Professor Hugh Perry, for detailing your exciting career journey and inspiring early career researchers to collaborate and work towards a common goal!