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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
.
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