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Infect. Immun., 05 1995, 1725-1731, Vol 63, No. 5
K Aguirre, EA Havell, GW Gibson and LL Johnson
Although naive C.B-17 and BALB/cBy mice die of meningoencephalitis within 5
weeks of intravenous infection with an opportunistic strain of Cryptococcus
neoformans, immunized mice express an acquired, CD4+ T- cell-dependent
immunity and survive an intravenous infection. Infusion of lymphocytes from
immune mice into severe combined immunodeficiency (SCID) mice renders these
mice more resistant to cryptococcal brain infection than uninfused
controls. We have investigated the role of gamma interferon (IFN-gamma) and
tumor necrosis factor (TNF) in acquired resistance to C. neoformans.
Neutralization of either IFN- gamma or TNF impaired resistance of immune
BALB/cBy or C.B-17 mice to cryptococci. At 10 days postinfection, there
were approximately 10 times as many yeast cells in the brains of mice
treated with either anticytokine antibody as in the brains of mice treated
with control antibody. Simultaneous neutralization of IFN-gamma and TNF
further exacerbated infection. Neutralization of IFN-gamma or TNF also
impaired resistance in immune lymphocyte-infused SCID mice, resulting in
significantly higher yeast burdens in brains of cytokine-neutralized mice
than in brains of controls. Concurrent neutralization of IFN-gamma and TNF
rendered SCID recipients of immune cells equivalent to uninfused SCID mice
with respect both to brain yeast burdens at 10 days and to survival.
Anti-TNF treatment alone also curtailed survival. Histological examination
of the brains of cytokine-neutralized mice revealed deficiencies in ability
to focus inflammatory cells at brain lesions. These data demonstrate that
both IFN-gamma and TNF are important mediators of acquired resistance to
cryptococcal meningoencephalitis.
Copyright © 1995, American Society for Microbiology
Role of tumor necrosis factor and gamma interferon in acquired resistance to Cryptococcus neoformans in the central nervous system of mice
Trudeau Institute, Saranac Lake, New York 12983, USA.
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