The Journal of Immunology,
Journal Year:
2015,
Volume and Issue:
195(5), P. 1939 - 1943
Published: July 30, 2015
Abstract
Detection
of
intracellular
DNA
triggers
activation
the
stimulator
IFN
genes–dependent
IFN-stimulatory
(ISD)
pathway,
which
is
essential
for
antiviral
immune
responses.
However,
chronic
this
pathway
implicated
in
autoimmunity.
Mutations
TREX1,
a
3′
repair
exonuclease
that
degrades
cytosolic
DNA,
cause
Aicardi–Goutières
syndrome
and
chilblain
lupus.
Trex1−/−
mice
develop
lethal,
IFN-driven
autoimmune
disease
dependent
on
ISD
but
sensors
detect
endogenous
accumulates
have
not
been
defined.
Multiple
proposed
to
activate
including
cyclic
GMP–AMP
synthase
(cGAS).
In
study,
we
show
lacking
cGAS
are
completely
protected
from
lethality,
exhibit
dramatically
reduced
tissue
inflammation,
fail
autoantibodies.
These
findings
implicate
as
key
driver
suggest
inhibitors
may
be
useful
therapeutics
related
diseases.
Military Medical Research,
Journal Year:
2020,
Volume and Issue:
7(1)
Published: March 13, 2020
Abstract
An
acute
respiratory
disease,
caused
by
a
novel
coronavirus
(SARS-CoV-2,
previously
known
as
2019-nCoV),
the
disease
2019
(COVID-19)
has
spread
throughout
China
and
received
worldwide
attention.
On
30
January
2020,
World
Health
Organization
(WHO)
officially
declared
COVID-19
epidemic
public
health
emergency
of
international
concern.
The
emergence
SARS-CoV-2,
since
severe
syndrome
(SARS-CoV)
in
2002
Middle
East
(MERS-CoV)
2012,
marked
third
introduction
highly
pathogenic
large-scale
into
human
population
twenty-first
century.
As
1
March
total
87,137
confirmed
cases
globally,
79,968
7169
outside
China,
with
2977
deaths
(3.4%)
had
been
reported
WHO.
Meanwhile,
several
independent
research
groups
have
identified
that
SARS-CoV-2
belongs
to
β-coronavirus,
identical
genome
bat
coronavirus,
pointing
natural
host.
uses
same
receptor,
angiotensin-converting
enzyme
2
(ACE2)
for
SARS-CoV,
mainly
spreads
through
tract.
Importantly,
increasingly
evidence
showed
sustained
human-to-human
transmission,
along
many
exported
across
globe.
clinical
symptoms
patients
include
fever,
cough,
fatigue
small
appeared
gastrointestinal
infection
symptoms.
elderly
people
underlying
diseases
are
susceptible
prone
serious
outcomes,
which
may
be
associated
distress
(ARDS)
cytokine
storm.
Currently,
there
few
specific
antiviral
strategies,
but
potent
candidates
antivirals
repurposed
drugs
under
urgent
investigation.
In
this
review,
we
summarized
latest
progress
epidemiology,
pathogenesis,
characteristics
COVID-19,
discussed
current
treatment
scientific
advancements
combat
coronavirus.
Annual Review of Immunology,
Journal Year:
2014,
Volume and Issue:
32(1), P. 513 - 545
Published: Feb. 20, 2014
Interferon-stimulated
gene
(ISG)
products
take
on
a
number
of
diverse
roles.
Collectively,
they
are
highly
effective
at
resisting
and
controlling
pathogens.
In
this
review,
we
begin
by
introducing
interferon
(IFN)
the
JAK-STAT
signaling
pathway
to
highlight
features
that
impact
ISG
production.
Next,
describe
ways
in
which
ISGs
both
enhance
innate
pathogen-sensing
capabilities
negatively
regulate
through
pathway.
Several
directly
inhibit
virus
infection
described
with
an
emphasis
those
early
late
stages
life
cycle.
Finally,
ongoing
efforts
identify
characterize
antiviral
ISGs,
provide
forward-looking
perspective
landscape.
Annual Review of Immunology,
Journal Year:
2017,
Volume and Issue:
35(1), P. 441 - 468
Published: Feb. 22, 2017
Microglia
are
resident
cells
of
the
brain
that
regulate
development,
maintenance
neuronal
networks,
and
injury
repair.
serve
as
macrophages
but
distinct
from
other
tissue
owing
to
their
unique
homeostatic
phenotype
tight
regulation
by
central
nervous
system
(CNS)
microenvironment.
They
responsible
for
elimination
microbes,
dead
cells,
redundant
synapses,
protein
aggregates,
particulate
soluble
antigens
may
endanger
CNS.
Furthermore,
primary
source
proinflammatory
cytokines,
microglia
pivotal
mediators
neuroinflammation
can
induce
or
modulate
a
broad
spectrum
cellular
responses.
Alterations
in
functionality
implicated
development
aging,
well
neurodegeneration.
Recent
observations
about
ontogeny
combined
with
extensive
gene
expression
profiling
novel
tools
study
biology
have
allowed
us
characterize
microglial
phenotypes
during
homeostasis,
disease.
In
this
article,
we
review
recent
advances
our
understanding
microglia,
contribution
involvement
Moreover,
highlight
complexity
targeting
therapeutic
intervention
neurodegenerative
diseases.
The Journal of Experimental Medicine,
Journal Year:
2018,
Volume and Issue:
215(5), P. 1287 - 1299
Published: April 5, 2018
Detection
of
microbial
DNA
is
an
evolutionarily
conserved
mechanism
that
alerts
the
host
immune
system
to
mount
a
defense
response
infections.
However,
this
detection
also
poses
challenge
as
how
distinguish
foreign
from
abundant
self-DNA.
Cyclic
guanosine
monophosphate
(GMP)-adenosine
(AMP)
synthase
(cGAS)
sensor
triggers
innate
responses
through
production
second
messenger
cyclic
GMP-AMP
(cGAMP),
which
binds
and
activates
adaptor
protein
STING.
cGAS
can
be
activated
by
double-stranded
irrespective
sequence,
including
Although
normally
kept
inactive
in
cells
still
not
well
understood,
recent
research
has
provided
strong
evidence
genomic
damage
leads
activation
stimulate
inflammatory
responses.
This
review
summarizes
findings
on
instability
trigger
serves
link
inflammation,
cellular
senescence,
cancer.
Science,
Journal Year:
2018,
Volume and Issue:
361(6403), P. 704 - 709
Published: July 5, 2018
The
binding
of
DNA
to
cyclic
GMP-AMP
synthase
(cGAS)
leads
the
production
secondary
messenger
(cGAMP),
which
activates
innate
immune
responses.
We
have
shown
that
cGAS
robustly
induced
formation
liquidlike
droplets
in
was
activated.
disordered
and
positively
charged
N
terminus
enhanced
cGAS-DNA
phase
separation
by
increasing
valencies
binding.
Long
more
efficient
promoting
liquid
enzyme
activity
than
short
DNA.
Moreover,
free
zinc
ions
both
vitro
cells
separation.
These
results
demonstrated
DNA-induced
transition
promotes
cGAMP
signaling.
