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Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model.
[allergic bronchopulmonary aspergillosis]
In
susceptible
individuals
,
exposure
to
Aspergillus
fumigatus
can
lead
to
the
development
of
atopic
lung
diseases
such
as
allergic
bronchopulmonary
aspergillosis
(
ABPA
)
and
severe
asthma
with
fungal
sensitization
(
SAFS
)
.
Protease
allergens
including
Asp
f
5
and
Asp
f
13
from
Aspergillus
fumigatus
,
are
thought
to
be
important
for
initiation
and
progression
of
allergic
asthma
.
To
assess
the
importance
of
secreted
protease
allergens
Asp
f
5
(
matrix
metalloprotease
)
and
Asp
f
13
(
serine
protease
)
in
Aspergillus
fumigatus
induced
inflammation
,
airway
hyperactivity
,
atopy
and
airway
wall
remodelling
in
a
murine
model
following
chronic
exposure
to
secreted
allergens
.
Methods
:
BALB
/
c
mice
were
repeatedly
intranasally
dosed
over
the
course
of
five
weeks
with
culture
filtrate
from
wild-
type
(
WT
)
,
Asp
f
5
null
(
∆
5
)
or
Asp
f
13
null
(
∆
13
)
strains
of
Aspergillus
fumigatus
.
Airway
hyperreactivity
was
measured
by
non-invasive
whole-body
plethysmography
,
Th
2
response
and
airway
inflammation
by
ELISA
and
cell
counts
,
whilst
airway
remodelling
was
assessed
by
histological
analysis
.
Parent
WT
and
∆
5
culture
filtrates
showed
high
protease
activity
,
whilst
protease
activity
in
∆
13
culture
filtrate
was
low
.
Chronic
intranasal
exposure
to
the
three
different
filtrates
led
to
comparable
airway
hyperreactivity
and
Th
2
response
.
However
,
protease
allergen
deleted
strains
,
in
particular
∆
13
culture
filtrate
,
induced
significantly
less
airway
inflammation
and
remodelling
compared
to
WT
culture
filtrate
.
Aspergillus
fumigatus
secreted
allergen
proteases
,
Asp
f
5
and
Asp
f
13
,
are
important
for
recruitment
of
inflammatory
cells
and
remodelling
of
the
airways
in
this
murine
model
.
However
,
deletion
of
a
single
allergen
protease
fails
to
alleviate
airway
hyperreactivity
and
allergic
immune
response
.
Targeting
protease
activity
of
Aspergillus
fumigatus
in
conditions
such
as
SAFS
or
ABPA
may
have
beneficial
effects
in
preventing
key
aspects
of
airway
pathology
.
This
article
is
protected
by
copyright
.
All
rights
reserved
.
Diseases
Validation
Diseases presenting
"th2 response and airway inflammation by elisa and cell counts"
symptom
allergic bronchopulmonary aspergillosis
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