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Limited role for ASC and NLRP3 during in vivo Salmonella Typhimurium infection.
[typhoid]
The
inflammasome
is
an
intracellular
protein
complex
triggered
by
exposure
to
intracellular
pathogens
,
its
components
or
other
endogenous
proteins
.
It
leads
to
the
activation
of
and
subsequent
release
of
proinflammatory
cytokines
such
as
IL
-
1
β
and
IL
-
18
.
S
.
Typhimurium
is
a
Gram
-negative
intracellular
bacterium
,
which
is
known
to
trigger
inflammasome
assembly
via
recognition
by
the
cytosolic
receptors
,
NLRP
3
and
NLRC
4
(
which
act
via
the
adaptor
protein
,
ASC
)
to
induce
cell
death
and
cytokine
release
.
We
sought
to
characterize
the
role
of
ASC
and
NLRP
3
in
two
different
murine
models
(
typhoid
and
colitis
)
of
systemic
Salmonella
infection
.
Release
of
the
inflammasome
cytokine
IL
-
18
was
hampered
in
Asc-
/
-
but
not
Nlrp
3
-
/
-
mice
(
background
C
5
7
BL
/
6
)
during
S
.
Typhimurium
infection
.
Unexpectedly
,
neither
ASC
nor
NLRP
3
played
a
significant
role
in
host
defense
against
S
.
Typhimurium
infection
,
as
reflected
by
equal
bacterial
counts
in
WT
,
Asc-
/
-
and
Nlrp
3
-
/
-
mice
at
all
time
points
,
in
both
the
typhoid
and
colitis
models
.
Proinflammatory
cytokine
levels
(
TNF
-α
,
IL
-
6
)
and
the
extent
of
hepatic
and
splenic
pathology
did
not
differ
between
groups
in
the
typhoid
model
.
In
the
colitis
model
small
differences
were
seen
with
regard
to
splenic
and
hepatic
inflammation
,
although
this
was
IL
-
18
independent
.
IL
-
18
release
was
reduced
in
Asc-
/
-
but
not
Nlrp
3
-
/
-
mice
during
S
.
Typhimurium
infection
.
Despite
this
reduction
,
bacterial
counts
,
cytokine
levels
and
histological
inflammation
did
not
differ
between
wild-
type
and
knockout
mice
in
either
model
.
Our
results
reveal
a
limited
role
for
ASC
and
NLRP
3
during
in
vivo
S
.
Typhimurium
infection
despite
its
role
in
cytokine
maturation
.
Diseases
Validation
Diseases presenting
"limited role"
symptom
alpha-thalassemia
typhoid
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