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Immune system overreaction linked to deadly flu in pregnancy

RMIT University

Researchers have discovered why influenza can lead to life-threatening complications during pregnancy, as Australia prepares for the flu season.

In most people, influenza stays in the upper respiratory tract – mainly the nose – and clears without spreading further.

But during pregnancy, the virus can extend beyond the lungs into the cardiovascular system, increasing the risk of severe complications for mothers and babies.

Using animal models, a new preclinical study reveals precisely why the virus can spill into the bloodstream during pregnancy, opening the door for targeted treatment.

Researchers identified a viral sensor in the immune system, known as TLR7, that can become overactive during pregnancy, amplifying inflammation and spreading disease into the bloodstream.

Blocking TLR7 could help protect developing babies by stopping the placenta from becoming overly inflamed during flu infection.

Lead by RMIT University, with collaborators from Adelaide University and Trinity College Dublin, the study is published in Science Advances.

Lead author Dr Stella Liong from RMIT’s School of Health and Biomedical Sciences said the discovery redefines how we think about infection during pregnancy.

“We identified a viral sensor that’s meant to help fight influenza but, in pregnancy, can become overactive and drive damaging inflammation throughout the body,” she said.

“The findings shift understanding of how respiratory viruses affect pregnancy, showing that harm is not caused by the virus directly reaching the foetus, but by an overactive maternal immune response that disrupts vascular function.

“With this new information, we can start to work out how to switch off this TLR7 sensor, which could help prevent the harmful inflammation that makes flu in pregnancy so dangerous.”

First author Dr Gemma Trollope, who completed the research during her studies at RMIT and is now at the Olivia Newton-John Cancer Research Institute, said the findings reinforce the need for disease prevention.

“The best defence against maternal flu complications is immunisation, so we hope this finding leads to stronger healthcare messaging and more prevention,” she said.

“We need to invest in developing pregnancy-safe therapies and to remind people that getting vaccinated against flu is safe at any stage of pregnancy.”

Earlier studies have shown that severe flu in pregnancy can have long‑term impacts on babies’ brain development, by inflaming blood vessels and reducing the flow of oxygen and nutrients from mother to baby.

This new study pinpoints the underlying cause of that damage, reshaping our understanding of flu‑related risk in pregnancy and opening the door to more targeted therapies.

RMIT co-lead author Professor Stavros Selemidis said future treatments could focus on the immune system rather than the virus itself.

“Our study shows that in pregnancy, the problem isn’t just the flu virus – it’s the immune system overreacting. That’s where future treatments could really make a difference,” he said.

“We’re ready to work with partners to help develop the next generation of therapies and clinical guidelines.”

The team is planning further research on how to target TLR7 to reduce the risk of severe influenza and pregnancy complications.

Organisations wishing to partner with RMIT can contact [email protected].

‘TLR7 alters the maternal immune landscape during influenza A infection to increase maternal and fetal morbidity’ is published in Science Advances. (DOI: 10.1126/sciadv.ady2382).

The research received funding from the National Health and Medical Research Council of Australia (grants 1122506, 1128276, 2002948).

Contact details:

RMIT External Affairs and Media, +61 439 704 077 or [email protected].