Acute Invasive Aspergillosis: The Mouse Makes the Difference

Ref ID: 5468

Author: Najvar L.K.1, Bocanegra R.1, Molina D.D.1, Mao-Wang Ho2, Vallor A.C.1, Kirkpatrick W.R.1, Patterson T.F.1, Graybill J.R.1

Author address:

1The University of Texas Health Science Center, San Antonio, TX, USA2China Medical University Hospital, Taichung, Taiwan

Full conference title:

2nd Advances against Aspergillosis


Background: Many models of invasive aspergillosis use intravenous
infection which heavily targets the spleen and kidneys and almost
completely spares the lungs. In contrast, clinical aspergillosis almost
invariably follows inoculation of the upper or lower respiratory tract
and the lungs are the most heavily targeted organs. Our group has
developed a model for murine invasive aspergillosis which reproduces
clinical pathogenesis (Sheppard, AAC 2004). However, the optimal animal
model, including mouse strain, and the methods of immune suppression to
facilitate the invasive fungal infection are still undergoing
definition. These parameters are explored in the present studies.
Methods: Outbred ICR, and inbred DBA, C57 and Balb/c mice were infected
with Aspergillus fumigatus #AF293 using two types of aerosol chambers.
The first is an acrylic chamber that allows simultaneous challenge of 50
mice. The second is a Madison chamber which allows simultaneous
challenge of >100 mice. In the acrylic chamber we nebulized conidia of
Aspergillus fumigatus at 10^9 CFU/ml of fluid for 1 h for infection and
in the Madison chamber we nebulized conidia at 10^10 CFU/ml for 1 h.
Mice were immunosuppressed with cortisone acetate and cyclophosphamide
on day -2 and day +3 of infection and treated with ceftazidime daily
beginning on day -2 before infection. The course of infection was
analyzed by length of survival (Log rank test, n=10-20) and
semi-quantitative tissue cultures (Mann Whitney test, n=5-20) done on
day 1, 3, 5, 7 and 11 after infection. Results: 1) Similar results were
obtained in mice infected with either chamber. 2) DBA mice were
unsatisfactory: immunocompetent DBA mice did not succumb following
infection nor did Aspergillus persist in their lungs; immunosuppressed
DBA mice succumbed by day 9, whether or not they were infected with
Aspergillus. 3) C57 mice were also unsatisfactory: they did not succumb
to aspergillosis and they rapidly reduced their lung tissue fungal
burden counts. 4) Both Balb/c and ICR mice were more satisfactory:
following infection with Aspergillus in the acrylic chamber mortality
was 60% and 10-40% (respectively) in the Madison chamber with both mouse
strains. Persistence of Aspergillus in their lungs occurred to day 11,
with approximately 10^4 total lung fungal burden/mouse with the acrylic
chamber and with persistent but lower counts using the Madison chamber.
Conclusions: For different reasons neither DBA nor C57 mice were
suitable models of invasive aspergillosis in this system. In contrast,
both outbred ICR and inbred Balb/c mice were acceptable models of
invasive aspergillosis particularly in the acrylic chamber. This should
reassure investigators who want to use an inexpensive, readily available
outbred mouse for studies of acute invasive aspergillosis.

Abstract Number: P019

Conference Poster: y

Slides: y

Conference Year: 2006

Link to conference website: NULL

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