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Journal of Clinical Microbiology, 06 1996, 1433-1439, Vol 34, No. 6
R Nawada, R Amitani, E Tanaka, A Niimi, K Suzuki, T Murayama and F Kuze
Aspergillus spp. occasionally cause invasive pulmonary aspergillosis
following noninvasive infection in patients with underlying
bronchopulmonary disorders regardless of their systemic immunological
conditions. We developed a murine model of invasive pulmonary aspergillosis
following an earlier stage, noninvasive Aspergillus infection. BALB/c mice
were inoculated intratracheally with agarose beads containing Aspergillus
fumigatus conidia. Two weeks after inoculation, half of the mice were
immunosuppressed with cortisone acetate. During a 4-week observation
period, the survival rate of infected immunosuppressed mice was
significantly lower (P < 0.01) than that of infected nonimmunosuppressed
mice. The number of CFU in the lungs gradually decreased in the
nonimmunosuppressed mice, whereas a time-related significant increase (P
< 0.05) of CFU was demonstrated in the immunosuppressed mice. In the
lungs of the nonimmunosuppressed mice, there was marked accumulation of
neutrophils, lymphocytes, and macrophages (in this order) around the
agarose beads in the bronchi. Aspergillus hyphae were surrounded by the
inflammatory cells and did not invade the lung parenchyma. In contrast, in
the immunosuppressed mice, Aspergillus hyphae proliferated markedly and
invaded the lung parenchyma after immunosuppression. In this model, the
two-dimensional extents of the lesions were also evaluated with an
image-processing system. Time-related increase of the area of peribronchial
necrotic lesions was significant (P < 0.05) after immunosuppression.
This model should therefore be useful for investigating the pathophysiology
of noninvasive Aspergillus infection and invasive pulmonary aspergillosis
and also for clarifying the mechanism of conversion to the invasive disease
from the noninvasive stage.
Copyright © 1996 by the American Society for Microbiology. All rights reserved.
Murine model of invasive pulmonary aspergillosis following an earlier stage, noninvasive Aspergillus infection
Department of Infection and Inflammation, Kyoto University, Japan.
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