bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 26, 2024
ABSTRACT
Coronavirus
disease
2019
(COVID-19),
caused
by
infection
with
the
enveloped
RNA
betacoronavirus,
SARS-CoV-2,
led
to
a
global
pandemic
involving
over
7
million
deaths.
Macrophage
inflammatory
responses
impact
COVID-19
severity;
however,
it
is
unclear
whether
macrophages
are
infected
SARS-CoV-2.
We
sought
identify
mechanisms
regulating
macrophage
expression
of
ACE2,
primary
receptor
for
and
determine
if
susceptible
productive
infection.
developed
humanized
ACE2
(
hACE2
)
mouse
whereby
cDNA
was
cloned
into
locus
under
control
native
promoter.
validated
susceptibility
mice
SARS-CoV-2
relative
wild-type
an
established
K18-hACE2
model
acute
fulminating
disease.
Intranasal
exposure
pulmonary
consolidations
cellular
infiltrate,
edema,
hemorrhage,
consistent
pneumonia,
yet
unlike
model,
survived
maintained
stable
weight.
Infected
also
exhibited
unique
plasma
chemokine,
cytokine,
growth
factor
signature
mice.
demonstrated
evidence
viral
replication
in
infiltrating
lung
macrophages,
vitro
revealed
transcriptional
profile
indicative
altered
ribosomal
processing
machinery
as
well
activated
antiviral
defense.
IL-1β-driven
NF-κB
transcription
important
mechanism
dynamic
upregulation,
promoting
Experimental
models
that
make
use
will
allow
mechanistic
insight
factors
can
either
promote
host
resilience
or
increase
worsening
severity
Science Translational Medicine,
Год журнала:
2022,
Номер
14(674)
Опубликована: Сен. 22, 2022
Obesity,
characterized
by
chronic
low-grade
inflammation
of
the
adipose
tissue,
is
associated
with
adverse
coronavirus
disease
2019
(COVID-19)
outcomes,
yet
underlying
mechanism
unknown.
To
explore
whether
severe
acute
respiratory
syndrome
2
(SARS-CoV-2)
infection
tissue
contributes
to
pathogenesis,
we
evaluated
COVID-19
autopsy
cases
and
deeply
profiled
response
SARS-CoV-2
in
vitro.
In
cases,
identified
RNA
adipocytes
an
inflammatory
infiltrate.
We
two
distinct
cellular
targets
infection:
a
subset
tissue-resident
macrophages.
Mature
were
permissive
infection;
although
macrophages
abortively
infected,
initiated
responses
within
both
infected
bystander
preadipocytes.
These
data
suggest
that
could
contribute
severity
through
replication
virus
induction
local
systemic
driven
Respiratory Research,
Год журнала:
2024,
Номер
25(1)
Опубликована: Июнь 1, 2024
Precision
Cut
Lung
Slices
(PCLS)
have
emerged
as
a
sophisticated
and
physiologically
relevant
ex
vivo
model
for
studying
the
intricacies
of
lung
diseases,
including
fibrosis,
injury,
repair,
host
defense
mechanisms.
This
innovative
methodology
presents
unique
opportunity
to
bridge
gap
between
traditional
in
vitro
cell
cultures
animal
models,
offering
researchers
more
accurate
representation
intricate
microenvironment
lung.
PCLS
require
precise
sectioning
tissue
maintain
its
structural
functional
integrity.
These
thin
slices
serve
invaluable
tools
various
research
endeavors,
particularly
realm
airway
diseases.
By
providing
controlled
microenvironment,
precision-cut
empower
dissect
comprehend
multifaceted
interactions
responses
within
tissue,
thereby
advancing
our
understanding
pulmonary
pathophysiology.
Nature Immunology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 22, 2025
Abstract
The
rapid
onset
of
innate
immune
defenses
is
critical
for
early
control
viral
replication
in
an
infected
host
and
yet
it
can
also
lead
to
irreversible
tissue
damage,
especially
the
respiratory
tract.
Sensitive
regulators
must
exist
that
modulate
inflammation,
while
controlling
infection.
In
present
study,
we
identified
acetylcholine
(ACh)-producing
B
cells
as
such
regulators.
are
most
prevalent
ACh-producing
leukocyte
population
tract
demonstrated
with
choline
acetyltransferase
(ChAT)-green
fluorescent
protein
(GFP)
reporter
mice,
both
before
after
infection
influenza
A
virus.
Mice
lacking
ChAT
cells,
disabling
their
ability
generate
ACh
(ChatBKO),
but
not
those
T
significantly,
selectively
directly
suppressed
α7-nicotinic-ACh
receptor-expressing
interstitial,
alveolar,
macrophage
activation
secrete
tumor
necrosis
factor
(TNF),
better
virus
at
1
d
postinfection.
Conversely,
TNF
blockade
via
monoclonal
antibody
treatment
increased
loads
time.
By
day
10
infection,
ChatBKO
mice
showed
local
systemic
inflammation
reduced
signs
lung
epithelial
repair
despite
similar
clearance.
Thus,
key
participants
immediate
regulatory
cascade
controls
damage
shifting
balance
toward
cost
enhanced
replication.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 31, 2024
Abstract
The
SARS-CoV-2
viral
infection
transforms
host
cells
and
produces
special
organelles
in
many
ways,
we
focus
on
the
replication
organelles,
sites
of
genomic
RNA
(vgRNA).
To
date,
precise
cellular
localization
key
molecules
intermediates
has
been
elusive
electron
microscopy
studies.
We
use
super-resolution
fluorescence
specific
labeling
to
reveal
nanoscopic
organization
that
contain
numerous
vgRNA
along
with
enzymes
clusters
double-stranded
(dsRNA).
show
are
organized
differently
at
early
late
stages
infection.
Surprisingly,
accumulates
into
distinct
globular
cytoplasmic
perinuclear
region,
which
grow
accommodate
more
as
time
increases.
endoplasmic
reticulum
(ER)
markers
nsp3
(a
component
double-membrane
vesicle,
DMV)
periphery
suggests
encapsulated
DMVs,
have
membranes
derived
from
ER.
These
merge
larger
vesicle
packets
advances.
Precise
co-imaging
nanoscale
vgRNA,
dsRNA,
proteins
may
inform
therapeutic
approaches
target
associated
processes.
Pathogens,
Год журнала:
2025,
Номер
14(1), С. 91 - 91
Опубликована: Янв. 17, 2025
The
lung
is
a
vital
organ
for
the
body
as
main
source
of
oxygen
input.
Importantly,
it
also
an
internal
that
has
direct
contact
with
outside
world.
Innate
immunity
protective
system
in
various
organs,
whereas,
case
lung,
helps
maintain
healthy,
functioning
cellular
and
molecular
environment
prevents
any
overt
damage
caused
by
pathogens
or
other
inflammatory
processes.
Disturbances
innate
properties
processes,
whether
over-responsiveness
process
triggered
lack
responses
due
to
dysfunctions
immune
cells
make
up
could
be
correlated
pathological
conditions.
In
this
review,
we
discuss
globally
how
components
are
important
not
only
maintaining
homeostasis
but
during
pathophysiology
notable
diseases
beyond
acute
pulmonary
infections,
including
chronic
obstructive
disease
(COPD),
asthma,
fibrosis.
Vaccines,
Год журнала:
2025,
Номер
13(3), С. 330 - 330
Опубликована: Март 20, 2025
CD169
is
a
sialic
acid-binding
immunoglobulin-like
lectin
(Siglec-1,
sialoadhesin)
that
expressed
by
subsets
of
tissue-resident
macrophages
and
circulating
monocytes.
This
receptor
interacts
with
α2,3-linked
Neu5Ac
on
glycoproteins
as
well
glycolipids
present
the
surface
immune
cells
pathogens.
CD169-expressing
exert
tissue-specific
homeostatic
functions,
but
they
also
have
opposing
effects
response.
CD169+
act
pathogen
filter,
protect
against
infectious
diseases,
enhance
adaptive
immunity,
at
same
time
pathogens
exploit
them
to
enable
further
dissemination.
In
cancer,
in
tumor-draining
lymph
nodes
are
correlated
better
clinical
outcomes.
inflammatory
expression
upregulated
monocytes
monocyte-derived
this
correlates
disease
state.
Given
their
role
promoting
currently
investigated
targets
for
vaccination
strategies
cancer.
review,
we
describe
studies
investigating
importance
several
settings
under
investigation.
