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Bottling immunity
New insights into therapies on tuberculosis are coming from the immune cells that already know how to control it
BY LYNN LOVE and ZACH VEILLEUX
For the two billion people worldwide with
latent tuberculosis infections, the clock is ticking. For them, the
TB bacteria are functioning as a terrorist sleeper cell would; they
are lying low until they can make a coordinated attack.
As Tom Ridge could tell you, it’s a
devilish strategy.
But Rockefeller scientists John MacMicking and
John McKinney plan to make use this insidious trait in the fight
against the disease. By studying how a healthy immune system
responds to the TB pathogen and keeps it in check, they’ve
identified a pathway that appears to inhibit its growth.
TB’s existence is based largely on
stealth. In 90 percent of those infected, it’s not life
threatening. People with these latent TB infections don’t
feel sick and they can’t spread the disease to others —
the body’s immune system is essentially holding the microbe at bay. But when the immune system
weakens, as happens with age or disease, the pathogen can surge to
life, triggering the full-blown respiratory meltdown that allows TB
to claim more human lives each year than any other bacterial
pathogen.
The immune system pathway discovered by
McKinney and MacMicking, called LRG-47, may explain the
body’s ability to hold TB at bay for as long as it does.
Studies of cells infected with TB suggest that the LRG-47 pathway
cuts off the bacteria’s ability to reproduce inside the
immune system cells where they hide. Though the precise mechanistic
details haven’t been worked out, there’s now powerful
evidence of this: In last week’s issue of the journal Science, MacMicking and
McKinney report that when the LRG-47 pathway is removed in
genetically engineered mice, the mice become profoundly susceptible to TB infection.
“By learning more about how the immune
system successfully operates during infection, we may be able to
manipulate the host-pathogen relationship in a way which favors
human health,” says MacMicking, a research associate in
McKinney’s Laboratory of Infection Biology.
“We’re looking for immune pathways which could render
the TB bacillus vulnerable.”
The current treatment for TB, a combination of
three potent antibiotics administered for six to nine months, is
physically and financially draining on patients and
downright prohibitive in developing countries with overburdened
healthcare systems. And when the full course of drugs isn’t
carefully followed, the bacteria build up resistance to the
antibiotics.
“This discovery is exciting because it
provides a much sought-after link between immune cell activation
and TB inhibition. LRG-47 opens up a new way of thinking about the
problem. It’s the first step in a biologic process which one
day could be mimicked chemically and therapeutically,” says
MacMicking.
October 31, 2003
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