White blood cells are picky about
sugar
CAMBRIDGE, Mass. (July 11, 2007) — Biology textbooks
are blunt—neutrophils are mindless killers. These
white blood cells patrol the body and guard against
infection by bacteria and fungi, identifying and destroying
any invaders that cross their path. But new evidence,
which may lead to better drugs to fight deadly pathogens,
indicates that neutrophils might actually distinguish
among their targets.
A scientist in the lab of Whitehead Member Gerald
Fink has discovered that neutrophils recognize and respond
to a specific form of sugar called beta-1,6-glucan on
the surface of fungi. This sugar comprises just a small
fraction of the fungal cell wall, much less than another
sugar with a slightly different chemical conformation
called beta-1,3-glucan. Because the scarce form of the
sugar elicits a much stronger reaction from immune cells
than the abundant one, it appears that neutrophils can
distinguish between two nearly identical chemicals.
“Previously, everyone thought that these
key cells of the immune system weren't picky
and would eat anything that looked foreign,” says
Whitehead Member Gerald Fink. “Ifat's
work has shown that the cells aren't little Pac-Men,
but can discriminate one pathogen from another.” |
“These results show that engulfment and killing
by neutrophils varies, depending on cell wall properties
of the microbe,” explains Whitehead postdoctoral
researcher Ifat Rubin-Bejerano, first author on the
paper, which appears online July 11 in the journal Cell
Host & Microbe. “We showed
that neutrophils respond in a completely different
way to slight changes in sugar composition. If we are
able to use this unique sugar to excite the immune
system, it may help the human body fight infection.”
“Previously, everyone thought that these key
cells of the immune system weren't picky and would
eat anything that looked foreign,” adds Fink,
who is also an MIT professor of biology. “Ifat's
work has shown that the cells aren't little Pac-Men,
but can discriminate one pathogen from another.”
Rubin-Bejerano had evidence that neutrophils respond
to beta-glucan. After coating tiny beads with a variety
of substances (including beta-1,3-glucan and beta-1,6-glucan),
she exposed them to the neutrophils and was surprised
to see a striking difference in their response to the
two sugars. The neutrophils quickly engulfed many of
the beads coated with beta-1,6-glucan, but only a few
of those covered in beta-1,3-glucan.
Previous studies indicated that blood serum (basically
blood minus cells) helps neutrophils recognize their
enemies, so Rubin-Bejerano decided to look for clues
to their response in this mixture. She identified several
proteins in serum that bind to beta-1,6-glucan, but
not beta-1,3-glucan, and then pinpointed a molecule
on the surface of the neutrophil that recognizes these
proteins.
To link her experiments back to real fungi, Rubin-Bejerano
worked with the pathogen Candida albicans, which
is the most common fungus in blood stream infections.
She used an enzyme to digest beta-1,6-glucan from the
fungal cell wall, leaving the beta-1,3-glucan intact.
She then unleashed the neutrophils on these altered
cells and observed a 50 percent reduction in the immune
response.
Our bodies maintain a fine balance between the immune
system and microbes. Antibiotics and antifungals tilt
the balance in favor of the immune system by targeting
the microbes directly. A substance like beta-1,6-glucan
could help tilt this balance further by stimulating
immune cells.
Rubin-Bejerano’s work offers hope for combating
the growing problem of microbial infections, which
can seriously threaten human health—particularly
in patients with compromised immune systems. In fact,
Rubin-Bejerano co-founded a company called ImmuneXcite
to explore this possibility.
This research is supported by the National Institutes
of Health. |
Neutrophils
generally ignore beads coated in beta-1,3-glucan [
