Frontiers in Immunology,
Год журнала:
2021,
Номер
12
Опубликована: Окт. 4, 2021
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
is
a
major
public
health
issue.
COVID-19
considered
an
airway/multi-systemic
disease,
and
demise
has
been
associated
with
uncontrolled
immune
response
cytokine
storm
in
to
the
virus.
However,
lung
pathology,
response,
tissue
damage
are
poorly
described
understood
due
safety
concerns.
Using
post-mortem
tissues
from
uninfected
deadly
cases
as
well
unbiased
combined
analysis
of
histology,
multi-viral
host
markers
staining,
correlative
microscopy,
confocal,
image
analysis,
we
identified
three
distinct
phenotypes
COVID-19-induced
damage.
First,
hemorrhage
characterized
by
minimal
infiltration
large
thrombus;
Second,
excessive
cell
but
no
hemorrhagic
events.
The
third
phenotype
correspond
combination
two
previous
ones.
We
observed
loss
alveolar
wall
integrity,
detachment
pieces,
fibroblast
proliferation,
extensive
fibrosis
all
phenotypes.
Although
studied
were
lethal
COVID-19,
strong
was
analyzed
significant
B
poor
T
infiltrations,
suggesting
exhausted
or
compromised
cellular
these
patients.
Overall,
our
data
show
that
SARS-CoV-2-induced
highly
heterogeneous.
These
individual
differences
need
be
understand
long-term
consequences.
Cell,
Год журнала:
2022,
Номер
185(5), С. 916 - 938.e58
Опубликована: Янв. 21, 2022
Treatment
of
severe
COVID-19
is
currently
limited
by
clinical
heterogeneity
and
incomplete
description
specific
immune
biomarkers.
We
present
here
a
comprehensive
multi-omic
blood
atlas
for
patients
with
varying
severity
in
an
integrated
comparison
influenza
sepsis
versus
healthy
volunteers.
identify
signatures
correlates
host
response.
Hallmarks
disease
involved
cells,
their
inflammatory
mediators
networks,
including
progenitor
cells
myeloid
lymphocyte
subsets,
features
the
repertoire,
acute
phase
response,
metabolism,
coagulation.
Persisting
activation
involving
AP-1/p38MAPK
was
feature
COVID-19.
The
plasma
proteome
enabled
sub-phenotyping
into
patient
clusters,
predictive
outcome.
Systems-based
integrative
analyses
tensor
matrix
decomposition
all
modalities
revealed
groupings
linked
specificity
compared
to
sepsis.
Our
approach
will
support
future
drug
development,
trial
design,
personalized
medicine
approaches
Abstract
Understanding
the
mechanism
that
leads
to
immune
dysfunction
in
severe
coronavirus
disease
2019
(COVID-19)
is
crucial
for
development
of
effective
treatment.
Here,
using
single-cell
RNA
sequencing,
we
characterized
peripheral
blood
mononuclear
cells
(PBMCs)
from
uninfected
controls
and
COVID-19
patients
paired
broncho-alveolar
lavage
fluid
(BALF).
We
found
a
close
association
decreased
dendritic
(DCs)
increased
monocytes
resembling
myeloid-derived
suppressor
(MDSCs),
which
correlated
with
lymphopenia
inflammation
patients.
Those
MDSC-like
were
immune-paralyzed.
In
contrast,
monocyte-macrophages
BALFs
produced
massive
amounts
cytokines
chemokines,
but
secreted
little
interferons.
The
frequencies
T
NK
significantly
patients,
especially
innate-like
various
CD8
+
cell
subsets,
compared
healthy
controls.
proportions
activated
CD4
subsets
among
compartment,
including
Th1,
Th2,
Th17-like
more
clonally
expanded
Patients’
showed
no
sign
exhaustion
or
augmented
death,
whereas
higher
levels
IFNG
,
TNF
CCL4
CCL5
etc.
Paired
TCR
tracking
indicated
abundant
recruitment
patients’
lung.
Together,
this
study
comprehensively
depicts
how
landscape
perturbed
COVID-19.
Nature Immunology,
Год журнала:
2021,
Номер
22(3), С. 322 - 335
Опубликована: Фев. 2, 2021
Immune
system
dysfunction
is
paramount
in
coronavirus
disease
2019
(COVID-19)
severity
and
fatality
rate.
Mucosal-associated
invariant
T
(MAIT)
cells
are
innate-like
involved
mucosal
immunity
protection
against
viral
infections.
Here,
we
studied
the
immune
cell
landscape,
with
emphasis
on
MAIT
cells,
cohorts
totaling
208
patients
various
stages
of
disease.
frequency
strongly
reduced
blood.
They
display
a
strong
activated
cytotoxic
phenotype
that
more
pronounced
lungs.
Blood
alterations
positively
correlate
activation
other
innate
proinflammatory
cytokines,
notably
interleukin
(IL)-18,
mortality
severe
acute
respiratory
syndrome
2
infection.
We
also
identified
monocyte/macrophage
interferon
(IFN)-α–IL-18
cytokine
shift
ability
infected
macrophages
to
induce
cytotoxicity
an
MR1-dependent
manner.
Together,
our
results
suggest
altered
functions
due
IFN-α–IL-18
imbalance
contribute
severity,
their
therapeutic
manipulation
may
prevent
deleterious
inflammation
COVID-19
aggravation.
Severe
characterized
by
hyperinflammation,
there
need
for
accurate
predictive
biomarkers
progression.
Lehuen
et
al.
demonstrate
show
dramatic
loss
those
do
remain
highly
state.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Ноя. 22, 2023
The
intricacy
of
diseases,
shaped
by
intrinsic
processes
like
immune
system
exhaustion
and
hyperactivation,
highlights
the
potential
renormalization
as
a
promising
strategy
in
disease
treatment.
In
recent
years,
our
primary
focus
has
centered
on
γδ
T
cell-based
immunotherapy,
particularly
pioneering
use
allogeneic
Vδ2
