Immune system component found common
to both humans and worms
Animal studies of innate immunity
may improve treatment of serious human disorders
BOSTON - July 25, 2002 - When someone gets a bacterial infection,
the human body mounts a complex set of reactions aimed at destroying
the invader. The role of what is called the innate immune system
- one of the most basic aspects of the overall immune response -
is to sound the alarm and jump start the body's response to pathogens.
Researchers have known that key components of innate immunity are
conserved across a variety of animals, and now scientists at Massachusetts
General Hospital (MGH) have shown that these same elements are used
by the lowly worm as well. The findings, published in the July 26
issue of Science,
suggest that scientists will now be better able to tease out the
details of innate immunity across a wide range of species.
"Innate immunity plays a central role in the initial encounter
with foreign pathogens and is thus critical to the host's defense
against infection," says co-lead author Dennis Kim, MD, PhD,
of the MGH Department of Molecular Biology. "But derangement
of the innate immune system is implicated in the pathogenesis of
overwhelming infections, as well as in chronic inflammatory diseases.
We anticipate that learning about fundamental aspects of the innate
immune system may lead to therapies for these conditions."
Because innate immunity is conserved among most animals, scientists
have been studying it in the laboratory using insect models. This
new report gives researchers another tool.
elegans nematode worm is more primitive than an
insect, and it's an excellent model organism that has provided scientists
with insights into development and other basic biological processes.
We hope that our study provides the basis for now using the worm
to study immune function," says principal investigator Frederick
Ausubel, PhD, of the MGH Department of Molecular Biology.
Ausubel's team has previously noted that human pathogens, such
as certain bacteria, can also kill C.
elegans. So Ausubel, Kim and co-lead author Rhonda Feinbaum,
PhD, also of MGH, set out to determine whether the immune responses
of these two organisms were similar. To do that, they looked for
worms that were immunocompromised or extra-susceptible to pathogens.
They identified two genetic mutations associated with this susceptibility
in genes that are part of a signaling pathway also known to be involved
in the innate immune response of humans.
"Because it's the only known component of the immune system
common to both C.
elegans and humans, this pathway probably represents
the most ancient aspect of innate immunity," says Ausubel.
"So our results validate the use of C.
elegans to study innate immunity, and insights gained
from the study of this pathway certainly will have human applications."
Kim says using the worm as a laboratory model for innate immunity
will not replace the utility of insect models. "Insects have
been very important in providing insights into innate immunity,"
he says. "We anticipate that the study of C.
elegans immunity will provide additional insights."
Other co-authors of the paper are Genevieve Alloing, PhD, Fred
Emerson, Danielle Garsin, PhD, and Man-Wah Tan, PhD, of the MGH
Department of Molecular Biology, and Hideko Inouo, Miho Tanaka-Hino,
Naoki Hisamoto, PhD, and Kunihiro Matsumoto, PhD, of Nagoya University
in Japan. The study was supported by grants from the National Institutes
of Health and from Advanced Research on Cancer of the Ministry of
Education, Culture, and Science of Japan.
The Massachusetts General Hospital, established in 1811, is the
original and largest teaching hospital of Harvard Medical School.
The MGH conducts the largest hospital-based research program in
the United States, with an annual research budget of more than $300
million and major research centers in AIDS, cardiovascular research,
cancer, cutaneous biology, transplantation biology and photomedicine.
In 1994, the MGH joined with Brigham and Women's Hospital to form
Partners HealthCare System, an integrated health care delivery system
comprising the two academic medical centers, specialty and community
hospitals, a network of physician groups and nonacute and home health
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials