HomeScience and ResearchScientific ResearchA protein that keeps the immune system from going crazy could lead...

A protein that keeps the immune system from going crazy could lead to new treatments

Published on

Immune response to infection is a finely tuned process. We require just enough action to eradicate the offending bacteria or viruses, but not enough to cause collateral damage to our own bodies.

In a study published in the Proceedings of the National Academy of Sciences, researchers at the University of California San Diego School of Medicine discovered that can act as a brake on macrophages.

Macrophages are front-line immune cells that detect pathogens and initiate an inflammatory response when necessary. Understanding how macrophages decide when to go all-out and when to stay calm is crucial for discovering new ways to strike the right balance, especially in cases where inflammation has gone too far, such as in sepsis, colitis, and other autoimmune disorders.

When the GIV gene was deleted from mouse macrophages, the immune cells rapidly became hypersensitive to even minute amounts of live bacteria or bacterial toxin. Mice with colitis and sepsis fared worse when their macrophages lacked the GIV gene.

Additionally, the researchers developed peptides that mimic GIV, allowing them to commandingly shut down mouse macrophages. The mice’s inflammatory response was tamed when they were treated with the GIV-mimic peptide.

“When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria,” said senior author Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center.

“It’s similar to what we’re seeing now with dangerous ‘cytokine storms’ that can result from infection with the novel coronavirus SARS-CoV-2. Macrophages, and the cytokines they produce, are the body’s own immune-stimulating agents and when produced in excessive amounts, they do more harm than good.”

Ghosh and colleagues discovered that the GIV protein normally associates with a molecule called Toll-like receptor 4 (TLR4). TLR4 is embedded directly into the cell membrane, with fragments poking both inside and outside the cell. TLR4 acts as an antenna outside the cell, searching for signs of invading pathogens. GIV is encased within the cell between the receptor’s two “feet.” When GIV is in place, the feet remain apart and nothing happens. When GIV is removed, the TLR4 feet come into contact with one another, initiating a cascade of immune-stimulating signals.

When Ghosh’s GIV-mimicking peptides are absent, they can act as a substitute for the protein, keeping the feet apart and calming macrophages.

“We were surprised at just how fluid the immune system is when it encounters a pathogen,” said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine.

“Macrophages don’t need to waste time and energy producing more or less GIV protein, they can rapidly dial their response up or down simply by moving it around, and it appears that such regulation happens at the level of gene transcription.”

Ghosh and colleagues intend to investigate the factors that influence whether the GIV brake remains in place while macrophages rest or is removed in response to a credible threat.

Photo By Alberto Ortega/Europa Press via Getty Images

Latest articles

For the First Time: Scientists Say They Have Found Lung Cancer’s Achilles’ Heel

An Entirely New Approach Makes Tumor Cells Easier To Destroy In a groundbreaking discovery, scientists...

This is Also True for Cannabis Vapes, According to a New Study

Is Vaping Cannabis Safe? Scientists Say the Risks May Be Different than Smoking In the...

‘Strong Evidence’: Low on This Vitamin Can Cut Several Years Off Life

The crucial vitamin for life and “the take-home message here is simple – the...

Goodbye to Gym? This Pill Mimics the Benefits of Exercise – Says New Study

Doctors have recommended exercise for years as a way to improve and maintain health....

More like this

For the First Time: Scientists Say They Have Found Lung Cancer’s Achilles’ Heel

An Entirely New Approach Makes Tumor Cells Easier To Destroy In a groundbreaking discovery, scientists...

This is Also True for Cannabis Vapes, According to a New Study

Is Vaping Cannabis Safe? Scientists Say the Risks May Be Different than Smoking In the...

‘Strong Evidence’: Low on This Vitamin Can Cut Several Years Off Life

The crucial vitamin for life and “the take-home message here is simple – the...