|Scientists Reveal How Disease Bacterium
Survives Inside Immune System Cell
New research on a bacterium that can survive encounters
with specific immune system cells has strengthened scientistsí belief
that these plentiful white blood cells, known as neutrophils,
dictate whether our immune system will permit or prevent
bacterial infections. A paper describing the research
was released today online in The Journal of Immunology.
Frank R. DeLeo, Ph.D., of Rocky Mountain Laboratories
(RML), part of the National Institute of Allergy and
Infectious Diseases (NIAID) of the National Institutes
of Health, directed the work at RML, in Hamilton, MT,
in collaboration with lead author Dori L. Borjesson,
D.V.M., Ph.D., of the University of Minnesota in St.
Scientists analyzed how neutrophils from healthy blood
donors respond to Anaplasma phagocytophilum, a tick-borne
bacterium that causes granulocytic anaplasmosis in people,
dogs, horses and cows. A. phagocytophilum is carried
by the same tick that transmits Lyme disease and was
first identified in humans in 1996. Human granulocytic
anaplasmosis (HGA) — formerly called human granulocytic
ehrlichiosis — is prevalent in Minnesota and along
the East Coast. HGA typically causes mild symptoms that
include fever, muscle aches and nausea. Some 362 U.S.
cases were reported to the Centers for Disease Control
and Prevention in 2003.
HGA is considered an emerging infectious disease, and
Dr. Borjesson is working to understand how it affects
blood cells — and neutrophils in particular. "Few people
know about this pathogen, but it is important because
it is transmitted by ticks and causes disease in both
animals and humans," Dr. Borjesson says.
Neutrophils, which make up about 60 percent of all
white blood cells, are the largest cellular component
of the human immune system — billions exist inside
each human. Typically, neutrophils ingest and then kill
harmful bacteria by producing molecules that are toxic
to cells, including a bleach-like substance called hypochlorous
acid. Once the bacteria are killed, the involved neutrophils
self-destruct in a process known as apoptosis. Recent
evidence suggests that this process is vital to resolving
A. phagocytophilum is unusual in that it can delay
apoptosis in human neutrophils, which presumably allows
some of the bacteria to replicate and cause infection.
"This particular bacterium specifically seeks out neutrophils
— possibly the most lethal of all host defense cells
— and remarkably, can alter their function, multiply
within them and thereby cause infection," says NIAID
Director Anthony S. Fauci, M.D.
Dr. DeLeo says the findings contrast with what is known
about other bacterial pathogens, most notably Staphylococcus
aureus, which is of great interest because of its increasing
resistance to antibiotic treatment. S. aureus, often
simply referred to as "staph," are bacteria commonly
found on the skin and in the noses of healthy people.
Occasionally, staph can cause infection; most are minor,
such as pimples, boils and other skin conditions. However,
staph bacteria can also cause serious and sometimes
fatal infections, such as bloodstream infections, surgical
wound infections and pneumonia.
In their experiments, the research team compared the
neutrophil response to A. phagocytophilum with that
of a weak strain of S. aureus. Using microarray technology
that allowed them to compare about 14,000 different
human genes, the researchers discovered how the response
to A. phagocytophilum deviates from that of S. aureus,
and thus permits the HGA agent to survive.
"This study has given us a global model of how bacteria
can inhibit neutrophil apoptosis," says Dr. DeLeo. "Our
next step is to look at specific human genes or gene
pathways within this model and try to determine which
of these molecules help prolong cell life following
infection." Information gathered from these and similar
studies, he adds, could help researchers develop therapeutics
to treat or prevent bacterial infections.
Other RML collaborators included Jovanka Voyich, Ph.D.,
and Scott Kobayashi, Ph.D., now an assistant professor
at the University of Idaho.
RML is part of the National Institutes of Health (NIH).
NIH is an agency of the U.S. Department of Health and
Human Services. NIAID supports basic and applied research
to prevent, diagnose and treat infectious diseases such
as HIV/AIDS and other sexually transmitted infections,
influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research
on transplantation and immune-related illnesses, including
autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Reference: D Borjesson et al.
"Insights into pathogen immune evasion mechanisms: Anaplasma
phagocytophilum fails to induce an apoptosis differentiation
program in human neutrophils." The Journal of