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Strong type 1, but impaired type 2, immune responses contribute to Orientia tsutsugamushi-induced pathology in mice.
[scrub typhus]
Scrub
typhus
is
a
neglected
,
but
important
,
tropical
disease
,
which
puts
one
-
third
of
the
world
's
population
at
risk
.
The
disease
is
caused
by
Orientia
tsutsugamushi
,
an
obligately
intracellular
Gram
-negative
bacterium
.
Dysregulation
in
immune
responses
is
known
to
contribute
to
disease
pathogenesis
;
however
,
the
nature
and
molecular
basis
of
immune
alterations
are
poorly
defined
.
This
study
made
use
of
a
newly
developed
murine
model
of
severe
scrub
typhus
and
focused
on
innate
regulators
and
vascular
growth
factors
in
O
.
tsutsugamushi-infected
liver
,
lungs
and
spleen
.
We
found
no
activation
or
even
reduction
in
base-line
expression
for
multiple
molecules
(
IL
-
7
,
IL
-
4
,
IL
-
13
,
GATA
3
,
ROR-γt
,
and
CXCL
12
)
at
2
,
6
and
10
days
post-infection
.
This
selective
impairment
in
type
2
-
related
immune
responses
correlated
with
a
significant
activation
of
the
genes
for
IL
-
1
β
,
IL
-
6
,
IL
-
10
,
TNF
-α
,
IFN-γ
,
as
well
as
CXCR
3
-
and
CXCR
1
-
related
chemokines
in
inflamed
tissues
.
The
elevated
angiopoietin
(
Ang
)
-
2
expression
and
Ang-
2
/
Ang-
1
ratios
suggested
excessive
inflammation
and
the
loss
of
endothelial
integrity
.
These
alterations
,
together
with
extensive
recruitment
of
myeloperoxidase
(
MPO
)
-
expressing
neutrophils
and
the
influx
of
CD
3
+
T
cells
,
contributed
to
acute
tissue
damage
and
animal
death
.
This
is
the
first
report
of
selective
alterations
in
a
panel
of
immune
regulators
during
early
O
.
tsutsugamushi
infection
in
intravenously
inoculated
C
5
7
BL
/
6
mice
.
Our
findings
shed
new
light
on
the
pathogenic
mechanisms
associated
with
severe
scrub
typhus
and
suggest
potential
targets
for
therapeutic
investigation
.
Diseases
Validation
Diseases presenting
"growth factors"
symptom
achondroplasia
alexander disease
aromatase deficiency
cholangiocarcinoma
dentin dysplasia
dentinogenesis imperfecta
dystrophic epidermolysis bullosa
kallmann syndrome
oligodontia
oral submucous fibrosis
primary effusion lymphoma
scrub typhus
severe combined immunodeficiency
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