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Axl receptor blockade protects from invasive pulmonary aspergillosis in mice.
[allergic bronchopulmonary aspergillosis]
Aspergillus
fumigatus
is
a
sporulating
fungus
found
ubiquitously
in
the
environment
,
which
is
quickly
contained
in
the
immunocompetent
host
but
can
cause
lethal
invasive
aspergillosis
in
the
immunocompromised
host
.
We
have
recently
demonstrated
that
Axl
(
one
member
of
the
Tyro
3
,
Axl
,
Mertk
receptor
family
)
is
a
key
regulator
of
antiviral
immune
responses
in
the
lung
.
In
this
study
,
we
investigated
the
role
of
Axl
in
antifungal
immunity
in
a
model
of
invasive
pulmonary
aspergillosis
(
IPA
)
.
In
this
model
,
Aspergillus
fumigatus
conidia
were
administered
into
the
lungs
of
neutrophil-depleted
mice
,
and
the
mice
were
monitored
for
survival
,
lung
inflammatory
response
,
and
fungal
clearance
.
The
lethal
effect
of
IPA
was
significantly
reduced
in
anti-
Axl
mAb-treated
mice
compared
with
IgG
control-treated
mice
.
Targeting
Axl
significantly
inhibited
pulmonary
inflammation
,
including
the
expression
of
IL
-
1
β
,
IL
-
6
,
TNF
-α
,
and
chitinase-like
proteins
in
whole
lung
.
Further
,
anti-
Axl
mAb
treatment
significantly
increased
M
1
macrophages
that
highly
expressed
inducible
NO
synthase
and
decreased
M
2
macrophages
that
expressed
Arginase
1
and
were
found
in
inflammatory
zone
protein
(
Fizz
1
)
.
More
importantly
,
anti-
Axl
mAb
treatment
significantly
increased
the
number
of
IFN-γ-producing
T
cells
and
NK
cells
compared
with
the
IgG
control
group
during
IPA
.
Together
,
our
results
demonstrate
that
the
Axl
mAb
treatment
is
protective
during
invasive
aspergillosis
in
neutropenic
mice
.
Collectively
,
these
data
suggest
a
potential
deleterious
role
for
Axl
during
primary
immune
responses
directed
against
A
.
fumigatus
and
novel
therapeutic
strategy
for
IPA
.
Diseases
Validation
Diseases presenting
"including the expression of il-1β"
symptom
allergic bronchopulmonary aspergillosis
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