New Discovery Identifies “Don’t Eat Me” Protein that Allows Lyme Bacteria to Evade Body’s Immune Response

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New Discovery Identifies “Don’t Eat Me” Protein that Allows Lyme Bacteria to Evade Body’s Immune Response

Stanford University/MIT/UCSF study funded by Bay Area Lyme Foundation offers new direction for tick-borne disease research, paving the way for potential new discoveries   

Palo Alto, CA, May 7, 2024—Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the U.S., today announced a study finding a new mechanism of immune evasion used by Borrelia burgdorferi (Bb), the bacterium that causes Lyme disease. This study is the first to identify the specific Borrelia protein that acts as a “don’t eat me” signal to the body’s immune system in people with Lyme disease, offering insight into how the bacteria may persist in Lyme patients and introduces an entirely new research direction toward potential future treatments. The research was conducted at Stanford University and University of California San Francisco and funded in part by Bay Area Lyme Foundation. This groundbreaking data posted on bioRxiv on April 30, 2024, is expected to be published in a peer-review journal in the future.

“One of the big mysteries of Lyme disease has been how Borrelia is able to evade and survive the immune system – and this study helps answer that question. We’ve unlocked a critical door to understanding how this bacteria, and possibly other pathogens, manage to trick the immune system to evade clearance,” said lead author Michal Tal, PhD, principal scientist, Massachusetts Institute of Technology, and a Bay Area Lyme Foundation 2018 Emerging Leader Award winner who has received additional funding from the organization for this project.

In this study, researchers found that P66, a known Borrelia surface protein and one of the IgG Western Blot testing “bands” used for diagnosis, can inhibit an important portion of the immune response.

“Patients need both a robust immune response and antibiotics to eradicate an infection – antibiotics alone are not usually sufficient. Addressing the mechanisms of immune evasion could help patients more efficiently eradicate the infection,” said Wendy Adams, research grant director, Bay Area Lyme Foundation, who also notes that persistent Lyme disease impacts more than two million Americans today.

Harmful bacteria entering the body are usually targeted by macrophages—immune cells which look for invaders to engulf and eliminate. However, this study shows that P66 is a bacterial “don’t eat me” signal encouraging the macrophage to ignore the bacteria by binding to a receptor on the macrophages’ surface called SIRP-alpha. This type of “don’t eat me” signal is a known mechanism in cancer and more recently, atherosclerosis. Specifically, the human “don’t eat me” signal protein CD47 binds the SIRP-alpha receptor on macrophages to signal that the cell shouldn’t be destroyed. Drugs that prevent CD47 from binding SIRP-alpha have been tested in clinical trials for the treatment of some cancers.

One of the study’s senior authors Irving Weissman, MD, professor and director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University and a Bay Area Lyme Foundation scientific advisory board member, explains that this study is a discovery of how an established protein can protect the bacteria with which it has co-evolved. These exciting and field-generating observations will have broad-reaching implications.

Dr. Weissman is renowned for his pioneering work in identifying “don’t eat me” proteins and his lab discovered all 4 known mammalian “don’t eat me proteins”: CD47, CD24, PDL1 and B2M. He is also the founder of companies which have developed or are developing therapeutics that target these mechanisms in cancer and atherosclerosis.

Researchers hope that blocking P66 activity, like blocking CD47’s activity in cancer, could help unleash the immune system in recognizing and fighting Borrelia bacteria.

“This work could extend beyond the Borrelia genus. Further investigation into whether other bacteria have “don’t eat me” signal protein mimics is crucial for understanding bacterial interactions with the immune system,” said second author Paige Hansen, Tal Research Group Researcher, Massachusetts Institute of Technology.

For the full text of the study, go here.

For more information about the mechanism of persistent infection, please see this review article in mBio.

“In an era where the pursuit of groundbreaking advancements in Lyme disease treatment is more crucial than ever, the Bay Area Lyme Foundation stands as a beacon of hope and efficacy. With a steadfast commitment to channeling 100% of all donations directly into research, BAL ensures the early identification and support of extraordinary scientific talent. This is a hugely impactful way for donors to maximize the effectiveness of their contributions towards conquering Lyme disease,” said Emily Fairbairn, a key donor to Bay Area Lyme Foundation, who together with Project Lyme and others made it possible for Bay Area Lyme Foundation to support this research.

About Lyme disease
The most common vector-borne infectious disease in the US, Lyme disease is a potentially disabling infection caused by bacteria transmitted through the bite of an infected tick to people and pets, and may also be passed from a pregnant mother to her unborn baby. If caught early, most cases of Lyme disease can be effectively treated, but it is commonly misdiagnosed due to a lack of awareness and inaccurate diagnostic tests. There are approximately 500,000 new cases of Lyme disease each year, according to statistics released in 2018 by the CDC. As a result of the difficulty in diagnosing and treating Lyme disease, up to two million Americans may be suffering from the impact of its debilitating long-term symptoms and complications, according to Bay Area Lyme Foundation estimates.

About Bay Area Lyme Foundation
Bay Area Lyme Foundation, a national organization committed to making Lyme disease easy to diagnose and simple to cure, is the leading public not-for-profit sponsor of innovative Lyme disease research in the US. A 501c3 organization based in Silicon Valley, Bay Area Lyme Foundation collaborates with world-class scientists and institutions to accelerate medical breakthroughs for Lyme disease. It is also dedicated to providing reliable, fact-based information so that prevention and the importance of early treatment are common knowledge. A pivotal donation from The LaureL STEM FUND covers overhead costs and allows for 100% of all donor contributions to the Bay Area Lyme Foundation to go directly to research and prevention programs. For more information about Lyme disease or to get involved, visit www.bayarealyme.org or call us at 650-530-2439.

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