“Do not eat me” protein–how Lyme survives the immune system

“Do not eat me” protein–how Lyme survives the immune system

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Bay Space Lyme Basis, a number one sponsor of Lyme disease analysis within the U.S., has introduced a research finding a new mechanism of immune evasion utilized by Borrelia burgdorferi (Bb), the bacterium that causes Lyme disease.

This research is the primary to determine the precise Borrelia protein that acts as a “don’t eat me” sign to the physique’s immune system in folks with Lyme disease.

This affords perception into how the micro organism could persist in Lyme sufferers and introduces a completely new analysis path towards potential future remedies.

The analysis was carried out at Stanford College and College of California San Francisco and funded partly by Bay Space Lyme Basis. This groundbreaking knowledge posted on bioRxiv on April 30, 2024, is anticipated to be printed in a peer-review journal sooner or later.

Evading the immune system

“One of many massive mysteries of Lyme disease has been how Borrelia is ready to evade and survive the immune system – and this research helps reply that query. We’ve unlocked a crucial door to understanding how this micro organism, and presumably different pathogens, handle to trick the immune system to evade clearance,” stated lead creator Michal Tal, PhD, principal scientist, Massachusetts Institute of Know-how.

Tal is a Bay Space Lyme Basis 2018 Rising Chief Award winner who has acquired further funding from the group for this venture.

On this research, researchers discovered that P66, a identified Borrelia floor protein and one of many IgG Western Blot testing “bands” used for analysis, can inhibit an vital portion of the immune response.

“Sufferers want each a strong immune response and antibiotics to eradicate an an infection – antibiotics alone are usually not normally enough. Addressing the mechanisms of immune evasion may assist sufferers extra effectively eradicate the an infection,” stated Wendy Adams, analysis grant director, Bay Space Lyme Basis, who additionally notes that persistent Lyme disease impacts greater than two million People right now.

The “don’t eat me” sign

Dangerous micro organism getting into the physique are normally focused by macrophages—immune cells which search for invaders to engulf and remove. Nevertheless, this research exhibits that P66 is a bacterial “don’t eat me” sign encouraging the macrophage to disregard the micro organism by binding to a receptor on the macrophages’ floor known as SIRP-alpha.

This kind of “don’t eat me” sign is a identified mechanism in most cancers and extra just lately, atherosclerosis. Particularly, the human “don’t eat me” sign protein CD47 binds the SIRP-alpha receptor on macrophages to sign that the cell shouldn’t be destroyed. Medicine that stop CD47 from binding SIRP-alpha have been examined in scientific trials for the remedy of some cancers.

One of many research’s senior authors Irving Weissman, MD, professor and director of the Institute for Stem Cell Biology and Regenerative Drugs at Stanford College and a Bay Space Lyme Basis scientific advisory board member, explains that this research is a discovery of how a longtime protein can defend the micro organism with which it has co-evolved. These thrilling and field-generating observations could have broad-reaching implications.

Dr. Weissman is famend for his pioneering work in figuring out “don’t eat me” proteins and his lab found all 4 identified mammalian “don’t eat me proteins”: CD47, CD24, PDL1 and B2M. He’s additionally the founding father of corporations which have developed or are growing therapeutics that focus on these mechanisms in most cancers and atherosclerosis.

Unleashing the immune system

Researchers hope that blocking P66 exercise, like blocking CD47’s exercise in most cancers, may assist unleash the immune system in recognizing and combating Borrelia micro organism.

“This work may lengthen past the Borrelia genus. Additional investigation into whether or not different micro organism have “don’t eat me” sign protein mimics is essential for understanding bacterial interactions with the immune system,” stated second creator Paige Hansen, Tal Analysis Group Researcher, Massachusetts Institute of Know-how.

Click here for the full text of the study.

For extra details about the mechanism of persistent an infection, please see this review article in mBio.

SOURCE: Bay Area Lyme Foundation

 

 



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