28 May 2010
Professor Charles Mackay believes a connection between the immune and metabolic systems might be causing the increase in certain inflammatory diseases such as asthma in western countries.
In this podcast, Professor Mackay, a 2010 Australia Fellow, tells NHMRC’s Carolyn Norrie that this discovery is potentially one of the most exciting things to happen in immunology. He explains that his Fellowship team’s investigations will cover a number of strands, including the immune-metabolic system connection, how newly discovered ‘helper’ T cells influence B cells, and how cells migrate around the body.
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Transcript of podcast
Voice-over: Welcome to this National Health and Medical Research Council podcast. Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.
Introduction: Hi, my name is Carolyn Norrie. I’m here today with Professor Charles Mackay talking to him about his work. Charles, congratulations on your Australia Fellowship.
Prof Mackay: Thank you.
Interviewer: Now you’ve been working in the area of immunology for quite some time, would you like to tell us about the work you do?
Prof Mackay: Yes, we try to understand basic immune mechanisms, why immune cells respond to antigens, but we also want to try to understand what goes wrong, particularly in autoimmune diseases and in asthma. And so we seek this basic understanding and we also want to develop new therapies for asthma and autoimmune diseases and so forth.
Interviewer: And what path is your work taking you down at the moment?
Prof Mackay: Several I think very, very interesting paths. One of those is the discovery of a new type of T cell that provides so called ‘help’ to a B cell and this is I think one of the important mechanisms for the production of antibodies that fight against diseases. And surprisingly, very little had been known about how this type of T cell worked and provided this help to B cells. And so we’ve played a role in identifying these cells and all of the molecules that this cell expresses and is responsible for this help for the stimulation of B cells to make antibodies against pathogens.
That’s one component of our work. Of course we have many components. Another very interesting component is to try and understand how cells migrate around the body. So for instance, a T cell or a white blood cell has to leave the blood and migrate through tissues to a site where a pathogen or maybe an inflammatory process is occurring. And this occurs through the use of chemo-attractant receptors that guide the cell through the tissue, and there’s a whole lot of little stimulating molecules that attract a cell from the blood and through the tissue. And so understanding the expression and the function of all of these molecules is something that we are intimately involved with.
Interviewer: So it sounds like the work you’re doing is both on the positive and the negative effects on the system?
Prof Mackay: Well, I think we view the immune system as finely balanced. We have to respond to pathogens, but we can’t respond too well because then the system can turn on itself, as what happens in autoimmune disease. And so, trying to understand what molecules are responsible for a positive response and what might be responsible for a negative response and what effects this fine balance is I think something that most immunologists are considering. And so there’s opportunities of course to perhaps boost an immune response so that we fight pathogens, and there’s also an opportunity to subdue an immune response so that we don’t get autoimmune diseases and asthma and so forth. But getting it right so you don’t go in one direction and have an adverse effect in the other is something that we have to be mindful of.
Interviewer: I understand that one of the avenues you’re looking into too is the role of diet and gastrointestinal microflora. Quite an interesting area?
Prof Mackay: Yes, I think that this is potentially, you know, one of the most exciting things to happen in immunology. This connection between the immune system and the metabolic system and our gut microbiota I just think has enormous potential and possibilities. And I personally believe it’s the entire basis for the increase in certain inflammatory conditions in western countries. Something about western society has led to these incredibly high levels of asthma and even in autoimmune diseases. And we know from various studies that it’s not industrialisation, because there were industrial countries that don’t get asthma, it’s something else to do with western society and I think it just has to be diet and I think very likely the effects of diet on the gut microbiota. And so we have identified – we’ve sought to identify – the mechanism for that and we believe a receptor we call GPR43 is one of these very important receptors that links the functioning of our immune system with what we eat.
Interviewer: It’s quite a radical thought I’m sure to many people?
Prof Mackay: It has been somewhat radical but then in another way it’s not that radical. It’s like traditional medical research where we study genes and molecules and mechanisms, almost catching up with some studies that have been done I suppose by more the fringe of medical research, people who have used, say, probiotics to look at effects on the immune system or the metabolic system and so forth. None of that research was really taken seriously, because there was never really hard core molecular mechanism. And so I think perhaps one of the things that’s been exciting I think about our research – and this research was accepted in Nature which is a very high profile journal – we’ve seen a convergence of these two sort of approaches of science into what I think is a really, really exciting development, this connection between metabolism, immunology and the gut microbiota.
Interviewer: Professor Charles Mackay thank you very much for speaking to us today.
Prof Mackay: Thanks, it’s been a pleasure.
Voice-over: This podcast was brought to you by the National Health and Medical Research Council, working to build a healthy Australia. You’ll find more information about this and other health and medical research issues on our website, at www.nhmrc.gov.au.