Study reveals strategy to enhance immune response to viral infections

The immune system, including T cells, is known to be compromised by severe viral infections and cancer, a condition known as immunological “burnout”. The development of new drugs for cancer or severe viral infections is mainly focused on overcoming immunological fatigue. Melbourne researchers have uncovered a strategy to improve the immune response in the face of severe viral infections, according to a study published in the journal ‘Immunity’.

A team from the Peter Doherty Institute of Infection and Immunity (Doherty Institute) led by Dr Sarah Gabriel of the University of Melbourne, Dr. Daniel Utzschneider and Professor Axel Kallies was able to identify why immune depletion occurs and how this can be overcome. The team had previously identified that while some T cells lost their function and burned out within days, others, called Tpex cells, were able to maintain their function over a long period of time.

‘This idea that you need to overcome depletion and improve your T cells is at the heart of immunotherapy,’ said Professor Kallies. “While immunotherapy works really well, it’s only effective in about 30 percent of people. By finding a way to prime T cells differently so they can function efficiently over the long term, we might be able to make the ‘immunotherapy more effective in more people,’ he added.

In their most recent paper published today in Immunity, the team have now identified a mechanism that explains how Tpex cells can maintain their physical form over long periods. Professor Kallies says the discovery has the potential to improve the success rate of immunotherapy.

“We found that the activity of mTOR, a nutrient sensor that coordinates cellular energy production and expenditure, is reduced in Tpex cells compared to those that were depleting,” said Dr. Gabriel. “This means that the TPEX cells were able to dampen their activity so they could stay functional longer. It’s like going slower to have the stamina to run a marathon instead of a full-speed sprint.”

Dr. Utzschneider emphasized that activating this switch to the immune system is a balancing act. “You don’t want to dampen the response too much to the point that the response becomes ineffective — you don’t want to be left to run amok,” said Dr. Utzschneider.

‘The next step was to find the mechanism that made this possible. We found that Tpex cells were exposed to higher amounts of an immunosuppressive molecule, TGF??, at the onset of an infection. This molecule essentially acts as a brake. reducing mTOR activity and thereby dampening the immune response.” Excitingly, the researchers were able to use this discovery to improve the immune response to a severe viral infection.

“When we treated the mice with an mTOR inhibitor early, this led to an improved immune response later during infection,” said Dr. Gabriel. “Moreover, mice that had been treated with the mTOR inhibitor responded better to checkpoint inhibition, a therapy widely used in cancer patients.” (ANI)

(This story has not been edited by Devdiscourse staff and is auto-generated from a syndicated feed.)

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