Cytokine Profile Analysis During Sialodacryoadenitis Virus and Mouse Hepatitis Virus JHM Strain Infection in Primary Mixed Microglia and Astrocyte Culture—Preliminary Research
Cells,
Год журнала:
2025,
Номер
14(9), С. 637 - 637
Опубликована: Апрель 25, 2025
The
Coronaviridae
family
has
again
demonstrated
the
potential
for
significant
neurological
complications
in
humans
during
recent
pandemic.
In
patients,
these
symptoms
persist
throughout
infection,
often
lasting
months.
consequences
of
most
post-infection
might
be
linked
with
abnormal
cytokine
production
and
reactive
oxygen
species
(ROS)
expression,
resulting
neuron
damage.
We
investigated
effect
infection
Mouse
Hepatitis
Virus
(MHV)
JHM
strain
Sialodacryoadenitis
(SDAV)
on
a
primary
microglia
astrocyte
culture
by
analysing
ROS
production,
chemokine
cell
death
one
month
post
infection.
For
this
purpose,
confocal
microscopy,
flow
cytometry,
high-throughput
Luminex
ProcartaPlex
immunopanel
48
cytokines
chemokines
were
utilised.
replication
MHV-JHM
SDAV
astrocytes
increased
pro-inflammatory
inhibited
anti-inflammatory
cytokines.
expression
induced
two
viruses
differed,
as
did
their
detection
after
resulted
much
broader
response
compared
to
that
MHV-JHM.
Both
significantly
levels
apoptosis
small
percentage
cells,
but
without
necrosis.
Язык: Английский
Neurotropic murine coronavirus mediated demyelination: Factors dampening pathogenesis
Journal of Neuroimmunology,
Год журнала:
2024,
Номер
393, С. 578382 - 578382
Опубликована: Июнь 1, 2024
Язык: Английский
Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families.
Antiviral Research,
Год журнала:
2024,
Номер
231, С. 106003 - 106003
Опубликована: Сен. 10, 2024
Язык: Английский
Lipopolysaccharide Enhances Microglia Antiviral Control of Betacoronavirus Infection through TLR4-Dependent Induction of IFNβ with Concomitant Modulation of dsRNA Sensors MDA5 and TLR3
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 30, 2024
Abstract
Microglia
play
a
pivotal
role
in
brain
homeostasis
and
are
essential
to
protective
immunity
within
the
central
nervous
system
by
coordinating
innate
immune
response
neuroinvasive
pathogens.
Bacterial
endotoxin
(lipopolysaccharide,
LPS)
is
most
used
pro-inflammatory
stimulus
for
microglia,
both
in
vitroand
vivo.
However,
impact
of
LPS
microglia
viral
infection,
including
coronaviruses
remains
ill-defined.
Murine
productively
infect
well
established
models
RNA
virus-induced
encephalitis
demyelination.
In
present
study,
we
investigated
effects
TLR4
stimulation
with
TLR4-specific
agonist
[smooth
(s)-form
(E.
coli
0111:B4)]
on
murine
coronavirus
MHV-JHM
-A59
infection
vitro.
Mechanistically,
our
data
revealed
that
restrict
replication
through
TLR4-dependent
induction
interferon
(IFN-b)
concomitant
modulation
dsRNA
sensors
melanoma
differentiation-associated
gene
5
(MDA5)
toll-like
receptor
3
(TLR3).
Moreover,
absence
induces
upregulation
MDA5
expression
activation
TLR3,
as
measured
phosphorylation
its
residue
Y759,
hallmark
TLR3
signaling
initiation.
Supporting
LPS-induced
activation,
demonstrated
selectively
contributes
TLR4-dependent,
neuroinflammation
even
virus
infection.
Overall,
study
provides
novel
mechanistic
insights
regarding
responses
highlights
previously
unrecognized
crosstalk
between
bacterial
implications
beyond
Язык: Английский
Microglia Morphological Response to Mesenchymal Stromal Cell Extracellular Vesicles Demonstrates EV Therapeutic Potential for Modulating Neuroinflammation
Kanupriya R. Daga,
Andrew M. Larey,
Maria G. Morfin
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 3, 2024
ABSTRACT
Background
Mesenchymal
stromal
cell
derived
extracellular
vesicles
(MSC-EVs)
are
a
promising
therapeutic
for
neuroinflammation.
MSC-EVs
can
interact
with
microglia,
the
resident
immune
cells
of
brain,
to
exert
their
immunomodulatory
effects.
In
response
inflammatory
cues,
such
as
cytokines,
microglia
undergo
phenotypic
changes
indicative
function
e.g.
morphology
and
secretion.
However,
these
in
not
well
understood.
Additionally,
no
disease-relevant
screening
tools
assess
MSC-EV
bioactivity
exist,
which
has
further
impeded
clinical
translation.
Here,
we
developed
quantitative,
high
throughput
morphological
profiling
approach
neuroinflammation-relevant
signals
whether
this
be
used
indicate
MSC-EVs.
Results
Using
an
immortalized
human
cell-line,
observed
increased
size
(perimeter,
major
axis
length)
complexity
(form
factor)
upon
stimulation
interferon-gamma
(IFN-γ)
tumor
necrosis
factor-alpha
(TNF-α).
Upon
treatment
MSC-EVs,
overall
score
(determined
using
principal
component
analysis)
shifted
towards
unstimulated
morphology,
indicating
that
bioactive
modulate
microglia.
The
effects
TNF-γ/IFN-α
stimulated
were
concomitant
reduced
secretion
14
chemokines/cytokines
(e.g.
CXCL6,
CXCL9)
12
CXCL8,
CXCL10).
Proteomic
analysis
lysates
revealed
significant
increases
192
proteins
HIBADH,
MEAK7,
LAMC1)
decreases
257
PTEN,
TOM1,
MFF)
treatment.
Of
note,
many
involved
regulation
migration.
Gene
Set
Variation
Analysis
upregulation
pathways
associated
response,
cytokine
production,
infiltration
T
cells,
NK
cells)
Semaphorin,
RHO/Rac
signaling).
mitochondrial
measured
suggesting
metabolism.
Conclusion
This
study
comprehensively
demonstrates
on
microglial
secretion,
cellular
proteome,
content.
Our
high-throughput,
rapid,
low-cost
enables
batches
manufacturing
conditions
enhance
EV
mitigate
functional
heterogeneity
disease
relevant
manner.
is
highly
generalizable
adapted
refined
based
selection
signal,
target
cell,
product.
Язык: Английский
Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation
Kanupriya R. Daga,
Andrew M. Larey,
Maria G. Morfin
и другие.
Journal of Biological Engineering,
Год журнала:
2024,
Номер
18(1)
Опубликована: Окт. 17, 2024
Mesenchymal
stromal
cell
derived
extracellular
vesicles
(MSC-EVs)
are
a
promising
therapeutic
for
neuroinflammation.
MSC-EVs
can
interact
with
microglia,
the
resident
immune
cells
of
brain,
to
exert
their
immunomodulatory
effects.
In
response
inflammatory
cues,
such
as
cytokines,
microglia
undergo
phenotypic
changes
indicative
function
e.g.
morphology
and
secretion.
However,
these
in
not
well
understood.
Additionally,
no
disease-relevant
screening
tools
assess
MSC-EV
bioactivity
exist,
which
has
further
impeded
clinical
translation.
Here,
we
developed
quantitative,
high
throughput
morphological
profiling
approach
neuroinflammation-
relevant
signals
whether
this
be
used
indicate
MSC-EVs.
Язык: Английский