3 months ago

An interview with Dr. Maureen McGargill on 'Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity'

Dr. Maureen McGargill

 

This content is part of the Research in Practice in Immunology series of interviews with scientists, focusing on how their research work can have impact on medical practice. Click here to follow 'Research in Practice in Immunology' - for free - on Researcher for more great interviews.


Maureen McGargill, an associate member at St. Jude Children's Hospital, speaks to Researcher about her research on the regulation of the immune response. Her research aims to eliminate pathogens and tumours without attacking healthy tissues effectively. And in particular, in regulation during viral infection, because when checkpoints fail during an infection, that can contribute to autoimmunity.

Can you tell us a little bit about your most recent paper? 

So in this paper, we were investigating whether antibodies that bind to more than one subtype of influenza – the goal of the universal influenza vaccine – can also bind to self-proteins. It's important to check to see if these antibodies that bind the conserved parts of influenza can also potentially bind self-proteins. Because a few recent reports showed that these antibodies that bind to more than one flu subtype could also be polyreactive, which means they can bind multiple distinct antigens, including self-proteins. And so, it was essential to test whether these antibodies can bind proteins that are relevant to human autoimmune disease and if they can contribute to the actual disease, even if they're generated. 

We used both a mouse model of influenza vaccination as well as humans that were infected with influenza. And we found that humans infected in 2009 during the swine flu pandemic; in 2022 generated more broadly reactive influenza antibodies compared to other influenza seasons. In addition, we found that individuals infected during this year also had more antibodies reactive against gangliosides, antibodies that are associated with Guillain-Barre Syndrome – an autoimmune disease where the immune system attacks peripheral nerves. It's associated with other infectious pathogens, but also potentially influenza. So we showed that humans that had more broadly reactive influenza antibodies also had more antibodies reactive to gangliosides. 

And in our mouse model of vaccination and infection, we showed that if you induce the generation of broadly reactive influenza antibodies, you also increase autoreactive antibodies. We identified several antibodies bound to the virus and self-proteins. 

And one of the crucial findings of the papers was that the presence of increased levels of these antibodies was associated with an increased autoimmune disease in four different mouse models. 

And I think one of the most important findings was when we took broadly reactive influenza antibodies or antibodies that bound one subtype of influenza and transferred those into other mice. We found that you don't get any increase in autoimmunity. But if you give additional inflammation or if there's an underlying genetic susceptibility to autoimmunity, then those broadly reactive influenza antibodies can contribute to disease. 

So the main conclusion is that these antibodies that can bind more than one influenza subtype do have the potential to bind self-proteins that are relevant to human autoimmune disease. And in the presence of excessive inflammation or genetic susceptibility to autoimmunity, they are additional factors that can contribute to autoimmune disease.

 

What are the implications of this research?

So multiple factors contribute to autoimmune disease, and we think, like many checkpoints, that would have to fail for an autoimmune disease to occur. And some factors that can contribute to the break of tolerance are diet, stress, and genetic susceptibility. But what our research shows us that high levels of broadly reactive influenza antibodies can also be another factor that can contribute to it. And so, the most important take-home message is that when designing strategies for universal influenza vaccines, it's essential to test whether those antibodies induced by those different protocols have an increased binding to self-proteins.

 

What outcome or aims are you looking for with your research?

We're currently trying to investigate the mechanisms that result in the generation of the autoreactive antibodies because our ultimate goal is to generate broadly reactive influenza antibodies that don't bind self-proteins. So that we can make safe and effective vaccines that would still protect against viruses that vary, suppose we're able to identify some of these mechanisms that result in the generation of the autoreactive antibodies. In that case, we might be able to prevent that from happening in a vaccine protocol.

 

Is there anything else you would like to add?

If you're trying to get the immune system to respond to parts of a virus that it normally doesn't make a durable immune response to, then it's particularly important to test the outcome of generating antibodies to these parts that our bodies normally naturally avoid. Also, not to say autoimmunity would happen to everybody. It's just one of the other factors contributing to a breakdown caused by multiple factors. So I guess I want to be careful not to say if you get a universal flu vaccine, you're going to get autoimmunity? No, it's just one of those additional things like stress or poor diet that can add up.

Self-protein refers to all proteins endogenously produced by DNA-level transcription and translation within an organism of interest.


You can read and discover Dr Maureen McGargill’s research here.

 

Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity is published in Cell Press

 

Photo Credits: St. Jude Children’s Research Hospital

Disclaimer: This is a transcript of a video conversation. You can listen to the recording on Researcher.

 

Publisher URL: https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00215-7

DOI: 7211.28975.cf42a017-554f-4c27-9917-ddbd72e37ee9.1655452258

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.