bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2020,
Volume and Issue:
unknown
Published: Sept. 1, 2020
Abstract
Infection
at
peripheral
sites,
such
as
the
skin,
activates
local
innate
immune
defenses
tasked
with
limiting
spread
of
pathogen
while
preserving
tissue
integrity.
T
cells
bearing
γδ
Cell
Receptors
(TCR),
which
comprise
multiple
phenotypically
distinct
subtypes
cells,
reside
in
normal
where
they
shape
immunity
to
cutaneous
infection,
prior
onset
an
adaptive
response
by
conventional
αβ
CD4
+
(T
CD4+
)
and
CD8
CD8+
cells.
The
mechanisms
used
control
virus
replication
pathology
following
infection
are
unknown,
so
we
examined
role
vaccinia
(VACV).
Resident
skin
expanded
combined
recruited
observed
after
VACV
infection.
However,
no
defect
or
increased
systemic
mice
lacking
despite
induction
a
cytolytic
specialized
subset
resident
While
examining
cell-mediated
identified
unique
wound
healing
signature
associated
that
has
features
common
to,
but
also
antagonize,
sterile
response.
Typically,
repair
is
thought
occur
only
clearance
pathogen,
viral
was
evident
peak
skin.
contributed
this
through
cytokines
growth
factors
required
for
efficient
closure.
Therefore,
early
mediators
likely
important
maintenance
barrier
function
prevention
secondary
bacterial
Author
Summary
among
first
cell
types
positioned
be
able
respond
it
assumed
these
play
similar
their
widespread
throughout
body,
namely
kill
infected
slow
spread.
found
Rather,
functioned
critical
component
previously
unrecognized
started
occurs
same
time
aims
clear
virus.
This
study
describe
both
response,
information
could
allow
manipulation
decrease
change
scarring
infections.
Journal of Leukocyte Biology,
Journal Year:
2016,
Volume and Issue:
100(5), P. 927 - 941
Published: June 24, 2016
Abstract
TLRs
play
a
critical
role
in
the
detection
of
microbes
and
endogenous
“alarmins”
to
initiate
host
defense,
yet
they
can
also
contribute
development
progression
inflammatory
autoimmune
diseases.
To
avoid
pathogenic
inflammation,
TLR
signaling
is
subject
multilayer
regulatory
control
mechanisms,
including
cooperation
with
coreceptors,
post-translational
modifications,
cleavage,
cellular
trafficking,
interactions
negative
regulators.
Nucleic
acid-sensing
are
particularly
interesting
this
regard,
as
both
recognize
host-derived
structures
require
internalization
their
ligand
result
intracellular
sequestration
nucleic
TLRs.
This
review
summarizes
mechanisms
TLRs,
regulation
access
ligands,
receptor
folding,
well
how
altered
mechanism
could
disorders.
Journal of Innate Immunity,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 13, 2024
The
re-emergence
of
the
Mpox
(formerly
monkeypox)
in
2022
non-endemic
countries
has
raised
many
concerns
for
global
health
due
to
its
high
transmissibility
and
mortality
rate.
A
major
challenge
fighting
is
ability
evade
host's
innate
immune
system,
which
first
line
defense
against
viral
infections.
encodes
various
proteins
that
interfere
with
key
antiviral
pathways
mechanisms,
such
as
nuclear
factor
kappa
B
(NF-κB)
signaling,
cytokine
production,
complement
inflammasome
activation,
chemokine
binding.
These
modulate
expression
function
mediators,
interferons,
interleukins,
toll-like
receptors,
impair
recruitment
activation
cells,
natural
killer
cells.
By
suppressing
or
altering
these
responses,
enhances
replication
infection
host
tissues
organs,
leading
systemic
inflammation,
tissue
damage,
organ
failure.
This
study
reveals
new
insights
into
molecular
cellular
interactions
between
host’s
immunity
identifies
potential
targets
strategies
interventions.
PLoS Pathogens,
Journal Year:
2017,
Volume and Issue:
13(6), P. e1006435 - e1006435
Published: June 14, 2017
The
goal
of
the
innate
immune
system
is
to
reduce
pathogen
spread
prior
initiation
an
effective
adaptive
response.
Following
infection
at
a
peripheral
site,
virus
typically
drains
through
lymph
node
entering
blood
stream
and
being
systemically
disseminated.
Therefore,
there
are
three
distinct
spatial
checkpoints
which
intervention
prevent
systemic
can
occur,
namely:
1)
site
infection,
2)
draining
via
filtration
or
3)
level
organs
that
filter
blood.
We
have
previously
shown
depletion
phagocytic
cells
allows
viral
after
dermal
with
Vaccinia
(VACV),
infects
naturally
skin.
Here
we
use
multiple
methodologies
define
both
checkpoint
identity
VACV.
Subcapsular
sinus
macrophages
been
implicated
as
critical
effectors
in
clearance
borne
viruses
following
infection.
find
monocyte
populations
recruited
VACV
play
role
control
local
pathogenesis
tissue
damage,
but
do
not
dissemination
virus.
virulent
VACV,
subcapsular
within
become
infected,
exclusively
required
spread.
Rather,
small
doses
enter
bloodstream
function
macrophages,
dendritic
cells,
further
results
illustrate
response
may
be
widespread
pathology
viruses,
such
poxviruses.
PLoS Pathogens,
Journal Year:
2019,
Volume and Issue:
15(10), P. e1007778 - e1007778
Published: Oct. 11, 2019
Type
I
interferons
(T1-IFN)
are
critical
in
the
innate
immune
response,
acting
upon
infected
and
uninfected
cells
to
initiate
an
antiviral
state
by
expressing
genes
that
inhibit
multiple
stages
of
lifecycle
many
viruses.
T1-IFN
triggers
production
Interferon-Stimulated
Genes
(ISGs),
activating
program
reduces
virus
replication.
The
importance
response
is
highlighted
evolution
viral
evasion
strategies
or
action
virus-infected
cells.
produced
via
activation
pathogen
sensors
within
cells,
a
process
targeted
virus-encoded
immunomodulatory
molecules.
This
probably
best
exemplified
prototypic
poxvirus,
Vaccinia
(VACV),
which
uses
at
least
6
different
mechanisms
completely
block
vitro.
Yet,
mice
lacking
aspects
signaling
often
more
susceptible
infection
with
viruses,
including
VACV,
than
wild-type
mice.
How
can
these
opposing
findings
be
rationalized?
cytosolic
DNA
sensor
cGAS
has
been
implicated
immunity
but
yet
linked
VACV
infection.
Indeed,
there
two
VACV-encoded
proteins
effectively
prevent
cGAS-mediated
T1-IFN.
We
find
majority
VACV-infected
vivo
do
not
produce
T1-IFN,
small
subset
utilize
sense
protect
protective
effect
mediated
ISG-mediated
control
Rather,
drives
increased
expression
CCL4,
recruits
inflammatory
monocytes
constrain
lesion
replication-independent
manner
limiting
spread
tissue.
Our
have
broad
implications
our
understanding
detection
vivo,
highlight
novel
strategy
Frontiers in Immunology,
Journal Year:
2020,
Volume and Issue:
11
Published: Feb. 28, 2020
Trained
innate
immunity
has
recently
emerged
as
a
novel
concept
of
immune
cells,
such
myeloid
exhibiting
memory
and
nonspecific
heterologous
to
protect
against
infections.
The
specificity
are
mediated
by
epigenetic,
metabolic,
functional
reprogramming
the
cells
progenitors
(and/or
NK
cells)
in
bone
marrow
peripheral
tissues
gut
lung
mucosa.
A
variety
agents,
BCG,
viruses,
their
components,
well
TLR
agonists,
cytokines
have
been
shown
be
involved
induction
trained
immunity.
Since
these
agents
widely
used
AIDS
vaccine
development
antigen
delivery
vectors
or
adjuvants,
cell
might
also
play
an
important
role
protecting
mucosal
virus
transmission
control
replication
major
reservoir.
Here
we
review
induced
vectors/adjuvants
that
studies
discuss
efficacy
possible
utilization
development.
Delineating
protective
effect
will
guide
design
vaccines.
PLoS Pathogens,
Journal Year:
2021,
Volume and Issue:
17(1), P. e1009215 - e1009215
Published: Jan. 13, 2021
Poxvirus
systems
have
been
extensively
used
as
vaccine
vectors.
Herein
a
RNA-Seq
analysis
of
intramuscular
injection
sites
provided
detailed
insights
into
host
innate
immune
responses,
well
expression
vector
and
recombinant
immunogen
genes,
after
vaccination
with
new
multiplication
defective,
vaccinia-based
vector,
Sementis
Copenhagen
Vector.
Chikungunya
Zika
virus
mRNA
protein
was
associated
necrosing
skeletal
muscle
cells
surrounded
by
mixed
cellular
infiltrates.
The
multiple
adjuvant
signatures
at
12
hours
post-vaccination
were
dominated
TLR3,
4
9,
STING,
MAVS,
PKR
the
inflammasome.
Th1
cytokine
IFNγ,
TNF
IL1β,
chemokine
CCL5
CXCL12.
Multiple
dendritic
cell
stimulation
evident.
By
day
seven,
transcripts
absent,
death,
neutrophil,
macrophage
inflammation
annotations
had
abated.
No
compelling
arthritis
identified.
Such
site
vaccinology
approaches
should
inform
refinements
in
poxvirus-based
design.
Viruses,
Journal Year:
2024,
Volume and Issue:
16(3), P. 425 - 425
Published: March 10, 2024
Infection
at
barrier
sites,
e.g.,
skin,
activates
local
immune
defenses
that
limit
pathogen
spread,
while
preserving
tissue
integrity.
Phenotypically
distinct
γδ
T
cell
populations
reside
in
where
they
shape
immunity
to
cutaneous
infection
prior
onset
of
an
adaptive
response
by
conventional
αβ
CD4+
(TCD4+)
and
CD8+
(TCD8+)
cells.
To
examine
the
mechanisms
used
cells
control
virus
replication
pathology,
we
examined
after
with
vaccinia
(VACV).
Resident
expanded
combined
recruited
pathology
VACV
infection.
However,
did
not
play
a
role
or
blockade
systemic
spread.
We
identified
unique
wound
healing
signature
has
features
common
to,
but
also
antagonize,
sterile
response.
Tissue
repair
generally
occurs
clearance
pathogen,
viral
started
peak
skin.
contributed
through
induction
multiple
cytokines/growth
factors
required
for
efficient
closure.
Therefore,
modulate
following
infection,
maintaining
skin
function
prevent
secondary
bacterial