New Discovery Identifies “Don’t Eat Me” Protein that Allows Lyme Bacteria to Evade Body’s Immune Response
May 07 2024 - 11:01AM
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:
https://bit.ly/3QyrRYa.
For more information about the mechanism of
persistent infection, please see this review article in mBio:
https://bit.ly/3JPavm8.
“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 diseaseThe 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 FoundationBay 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.
Media contact: Tara DiMilia Phone:
908-369-7168 Tara.DiMilia@tmstrat.com