2009-ASCB-Press-Book - page 11

T h e A m e r i c a n s o c i e t y f o r C e l l B i o l o g y
News from
The American Society
for Cell Biology
49th Annual Meeting
San Diego, CA
December 5–9, 2009
Fear the titans
10:00 am, U.S. Pacific Time
Sunday, December 6, 2009
Kirsten Nielsen
University of Minnesota
420 Delaware St., SE,
MMC1 196,
Minneapolis, MN 55455
(612) 625-4979
Author presents
Tuesday, December 8, 2009
11:00 am–12:30 pm
Poster Session 3:
Host-Pathogen Interactions III
Program 1720
Board B99;
Exhibit Halls D–H
Cryptococcal Cell Morphology
Affects Host Cell Interactions
and Pathogenicity
L. Okagaki, A.K. Strain,
K. Nielsen
Microbiology, University of
Minnesota, Minneapolis, MN
The discovery of cellular giants
among opportunistic fungi may
explain why cryptoccocal infection
remains the leading AIDS-related
cause of death on Earth
ryptococcus neoformans
is a for-
midable enemy. An encapsulated
is a classic
opportunistic infection that begins in the
lungs but can spread to the brain, caus-
ing meningitis. It strikes most often at
those with impaired immune systems.
Transplant recipients and chemotherapy
patients are vulnerable, but
infection has become a signature com-
plication of human immunodeficiency
virus/AIDS. In the U.S., infections spiked
in the mid-1990s, but in parts of Africa
cryptoccocal infection is still the AIDS-
defining condition and the leading cause
of AIDS-related death. Worldwide,
cryptoccocal meningitis is now killing
more than 1 million people every year.
Kirsten Nielsen and colleagues at the
University of Minnesota have now made
a bizarre discovery about
that can only add to its savage reputation.
It is literally a giant among infectious
fungi. The Nielsen lab has identified a
new cell type called “titans,” produced
in the lungs. Titans can
be up to 10 times larger than normal
cryptococcal cells and much larger than
host immune cells.
Nielsen was following up on earlier
reports of enlarged cells in human cryp-
toccocal infections, yet the identity of
these big cells and their role in virulence
was unknown. Using a mouse inhalation
model of
Nielsen looked
at the changes in cell shape and how
the emergence of titans sped up disease
progression. The titans are singularly
resistant to the host’s immune system,
especially macrophages, and can slow the
cells’ attempts to quarantine and kill the
intruders—all of which may explain how
the initial infection develops in the lungs
and why it is difficult to eradicate once
Nielsen says that to produce these
unusually large titan cells,
has evolved a system to recognize the
lung environment and then to generate
four or eight copies of its genome without
entering cell division. These redundant
copies of the genome may bulk up the
titan cell and strengthen its resistance to
host killing.
Titan cell formation by
is an important first step in the infec-
tion, Nielsen believes. Developing drugs
to specifically block titan cell formation
could prevent the progression to deadly
Cryptococcus titan cells (red) and normal cryptococcal
cells (green) interacting with host immune cells (gray).
One of the normal cells has been engulfed by the host
cell for killing, whereas the titan cells are too large for
the host cells.
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