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Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway.
[scrub typhus]
Dendritic
cells
(
DCs
)
orchestrate
host
defenses
against
microorganisms
.
In
infectious
diseases
due
to
intracellular
bacteria
,
the
inefficiency
of
the
immune
system
to
eradicate
microorganisms
has
been
attributed
to
the
hijacking
of
DC
functions
.
In
this
study
,
we
selected
intracellular
bacterial
pathogens
with
distinct
lifestyles
and
explored
the
responses
of
monocyte-derived
DCs
(
moDCs
)
.
Using
lipopolysaccharide
as
a
control
,
we
found
that
Orientia
tsutsugamushi
,
the
causative
agent
of
scrub
typhus
that
survives
in
the
cytosol
of
target
cells
,
induced
moDC
maturation
,
as
assessed
by
decreased
endocytosis
activity
,
the
ability
to
induce
lymphocyte
proliferation
and
the
membrane
expression
of
phenotypic
markers
.
In
contrast
,
Coxiella
burnetii
,
the
agent
of
Q
fever
,
and
Brucella
abortus
,
the
agent
of
brucellosis
,
both
of
which
reside
in
vacuolar
compartments
,
only
partly
induced
the
maturation
of
moDCs
,
as
demonstrated
by
a
phenotypic
analysis
.
To
analyze
the
mechanisms
used
by
C
.
burnetii
and
B
.
abortus
to
alter
moDC
activation
,
we
performed
microarray
and
found
that
C
.
burnetii
and
B
.
abortus
induced
a
specific
signature
consisting
of
TLR
4
,
TLR
3
,
STAT
1
and
interferon
response
genes
.
These
genes
were
down-modulated
in
response
to
C
.
burnetii
and
B
.
abortus
but
up-modulated
in
moDCs
activated
by
lipopolysaccharide
and
O
.
tsutsugamushi
.
This
transcriptional
alteration
was
associated
with
the
defective
interferon-β
production
.
This
study
demonstrates
that
intracellular
bacteria
specifically
affect
moDC
responses
and
emphasizes
how
C
.
burnetii
and
B
.
abortus
interfere
with
moDC
activation
and
the
antimicrobial
immune
response
.
We
believe
that
comparing
infection
by
several
bacterial
species
may
be
useful
for
defining
new
pathways
and
biomarkers
and
for
developing
new
treatment
strategies
.
Diseases
Validation
Diseases presenting
"fever"
symptom
22q11.2 deletion syndrome
acute rheumatic fever
alexander disease
allergic bronchopulmonary aspergillosis
canavan disease
carcinoma of the gallbladder
child syndrome
congenital toxoplasmosis
cushing syndrome
cystinuria
dracunculiasis
erdheim-chester disease
esophageal adenocarcinoma
esophageal carcinoma
familial mediterranean fever
focal myositis
hodgkin lymphoma, classical
lamellar ichthyosis
legionellosis
locked-in syndrome
malignant atrophic papulosis
neonatal adrenoleukodystrophy
neuralgic amyotrophy
oculocutaneous albinism
papillon-lefèvre syndrome
pyomyositis
pyruvate dehydrogenase deficiency
scrub typhus
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
typhoid
waldenström macroglobulinemia
wolf-hirschhorn syndrome
This symptom has already been validated