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Eosinophil deficiency compromises lung defense against Aspergillus fumigatus.
[allergic bronchopulmonary aspergillosis]
Exposure
to
the
mold
Aspergillus
fumigatus
may
result
in
allergic
bronchopulmonary
aspergillosis
,
chronic
necrotizing
pulmonary
aspergillosis
,
or
invasive
aspergillosis
(
IA
)
,
depending
on
the
host
's
immune
status
.
Neutrophil
deficiency
is
the
predominant
risk
factor
for
the
development
of
IA
,
the
most
life-threatening
condition
associated
with
A
.
fumigatus
exposure
.
Here
we
demonstrate
that
in
addition
to
neutrophils
,
eosinophils
are
an
important
contributor
to
the
clearance
of
A
.
fumigatus
from
the
lung
.
Acute
A
.
fumigatus
challenge
in
normal
mice
induced
the
recruitment
of
CD
11
b
+
Siglec
F
+
Ly-
6
G
(
lo
)
Ly-
6
C
(
neg
)
CCR
3
+
eosinophils
to
the
lungs
,
which
was
accompanied
by
an
increase
in
lung
Epx
(
eosinophil
peroxidase
)
mRNA
levels
.
Mice
deficient
in
the
transcription
factor
dblGATA
1
,
which
exhibit
a
selective
deficiency
in
eosinophils
,
demonstrated
impaired
A
.
fumigatus
clearance
and
evidence
of
germinating
organisms
in
the
lung
.
Higher
burden
correlated
with
lower
mRNA
expression
of
Epx
(
eosinophil
peroxidase
)
and
Prg
2
(
major
basic
protein
)
as
well
as
lower
interleukin
1
β
(
IL
-
1
β
)
,
IL
-
6
,
IL
-
17
A
,
granulocyte
colony-stimulating
factor
(
G-CSF
)
,
granulocyte-macrophage
colony-stimulating
factor
(
GM
-CSF
)
,
and
CXCL
1
levels
.
However
,
examination
of
lung
inflammatory
cell
populations
failed
to
demonstrate
defects
in
monocyte
/
macrophage
,
dendritic
cell
,
or
neutrophil
recruitment
in
dblGATA
1
-
deficient
mice
,
suggesting
that
the
absence
of
eosinophils
in
dlbGATA
1
-
deficient
mice
was
the
sole
cause
of
impaired
lung
clearance
.
We
show
that
eosinophils
generated
from
bone
marrow
have
potent
killing
activity
against
A
.
fumigtaus
in
vitro
,
which
does
not
require
cell
contact
and
can
be
recapitulated
by
eosinophil
whole-cell
lysates
.
Collectively
,
our
data
support
a
role
for
eosinophils
in
the
lung
response
after
A
.
fumigatus
exposure
.
Diseases
Validation
Diseases presenting
"a"
symptom
allergic bronchopulmonary aspergillosis
congenital adrenal hyperplasia
focal myositis
pleomorphic liposarcoma
pyruvate dehydrogenase deficiency
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