EMBO Molecular Medicine,
Год журнала:
2020,
Номер
12(12)
Опубликована: Окт. 20, 2020
In
patients
infected
by
SARS-CoV-2
who
experience
an
exaggerated
inflammation
leading
to
pneumonia,
monocytes
likely
play
a
major
role
but
have
received
poor
attention.
Thus,
we
analyzed
peripheral
blood
from
with
COVID-19
pneumonia
and
found
that
these
cells
show
signs
of
altered
bioenergetics
mitochondrial
dysfunction,
had
reduced
basal
maximal
respiration,
spare
respiratory
capacity,
decreased
proton
leak.
Basal
extracellular
acidification
rate
was
also
diminished,
suggesting
capability
perform
aerobic
glycolysis.
Although
ability
oxidative
burst,
they
were
still
capable
producing
TNF
IFN-γ
in
vitro.
A
significantly
high
amount
depolarized
mitochondria
abnormal
ultrastructure.
redistribution
monocyte
subsets,
significant
expansion
intermediate/pro-inflammatory
cells,
amounts
immature
found,
along
concomitant
compression
classical
monocytes,
increased
expression
inhibitory
checkpoints
like
PD-1/PD-L1.
High
plasma
levels
several
inflammatory
cytokines
chemokines,
including
GM-CSF,
IL-18,
CCL2,
CXCL10,
osteopontin,
finally
confirm
the
importance
immunopathogenesis.
Science,
Год журнала:
2020,
Номер
369(6508), С. 1210 - 1220
Опубликована: Авг. 11, 2020
Coronavirus
disease
2019
(COVID-19)
represents
a
global
crisis,
yet
major
knowledge
gaps
remain
about
human
immunity
to
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2).
We
analyzed
immune
responses
in
76
COVID-19
patients
and
69
healthy
individuals
from
Hong
Kong
Atlanta,
Georgia,
United
States.
In
the
peripheral
blood
mononuclear
cells
(PBMCs)
of
patients,
we
observed
reduced
expression
leukocyte
antigen
class
DR
(HLA-DR)
proinflammatory
cytokines
by
myeloid
as
well
impaired
mammalian
target
rapamycin
(mTOR)
signaling
interferon-α
(IFN-α)
production
plasmacytoid
dendritic
cells.
By
contrast,
detected
enhanced
plasma
levels
inflammatory
mediators-including
EN-RAGE,
TNFSF14,
oncostatin
M-which
correlated
with
severity
increased
bacterial
products
plasma.
Single-cell
transcriptomics
revealed
lack
type
I
IFNs,
HLA-DR
COVID-19,
transient
IFN-stimulated
genes.
This
was
consistent
bulk
PBMC
transient,
low
IFN-α
during
infection.
These
results
reveal
mechanisms
potential
therapeutic
targets
for
COVID-19.
Science,
Год журнала:
2021,
Номер
371(6529), С. 595 - 602
Опубликована: Фев. 4, 2021
Anti-programmed
cell
death
protein
1
(PD-1)
therapy
provides
long-term
clinical
benefits
to
patients
with
advanced
melanoma.
The
composition
of
the
gut
microbiota
correlates
anti-PD-1
efficacy
in
preclinical
models
and
cancer
patients.
To
investigate
whether
resistance
can
be
overcome
by
changing
microbiota,
this
trial
evaluated
safety
responder-derived
fecal
transplantation
(FMT)
together
PD-1-refractory
This
combination
was
well
tolerated,
provided
benefit
6
15
patients,
induced
rapid
durable
perturbation.
Responders
exhibited
increased
abundance
taxa
that
were
previously
shown
associated
response
anti-PD-1,
CD8
Abstract
The
recent
boom
in
microfluidics
and
combinatorial
indexing
strategies,
combined
with
low
sequencing
costs,
has
empowered
single-cell
technology.
Thousands—or
even
millions—of
cells
analyzed
a
single
experiment
amount
to
data
revolution
biology
pose
unique
science
problems.
Here,
we
outline
eleven
challenges
that
will
be
central
bringing
this
emerging
field
of
forward.
For
each
challenge,
highlight
motivating
research
questions,
review
prior
work,
formulate
open
This
compendium
is
for
established
researchers,
newcomers,
students
alike,
highlighting
interesting
rewarding
problems
the
coming
years.
Nature Communications,
Год журнала:
2020,
Номер
11(1)
Опубликована: Июль 6, 2020
Abstract
The
immune
system
of
patients
infected
by
SARS-CoV-2
is
severely
impaired.
Detailed
investigation
T
cells
and
cytokine
production
in
affected
COVID-19
pneumonia
are
urgently
required.
Here
we
show
that,
compared
with
healthy
controls,
patients’
cell
compartment
displays
several
alterations
involving
naïve,
central
memory,
effector
memory
terminally
differentiated
cells,
as
well
regulatory
PD1
+
CD57
exhausted
cells.
Significant
exist
also
lineage-specifying
transcription
factors
chemokine
receptors.
Terminally
from
proliferate
less
than
those
whereas
their
mitochondria
functionality
similar
CD4
both
groups.
Patients
display
significant
increases
proinflammatory
or
anti-inflammatory
cytokines,
including
helper
type-1
type-2
chemokines
galectins;
lymphocytes
produce
more
tumor
necrosis
factor
(TNF),
interferon-γ,
interleukin
(IL)-2
IL-17,
the
last
observation
implying
that
blocking
IL-17
could
provide
a
novel
therapeutic
strategy
for
COVID-19.
