GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18
PLoS Pathogens,
Journal Year:
2025,
Volume and Issue:
21(2), P. e1012654 - e1012654
Published: Feb. 3, 2025
Neutrophils
are
critical
for
host
defense
against
fungi.
However,
the
short
life
span
and
lack
of
genetic
tractability
primary
human
neutrophils
has
limited
in
vitro
analysis
neutrophil-fungal
interactions.
Human
induced
pluripotent
stem
cell
(iPSC)-derived
(iNeutrophils)
provide
a
genetically
tractable
system
to
study
responses
neutrophils.
Here,
we
show
that
deletion
transcription
factor
GATA1
from
iPSCs
results
iNeutrophils
with
improved
antifungal
activity
Aspergillus
fumigatus.
GATA1-knockout
(KO)
have
increased
maturation,
pattern
recognition
receptor
expression
neutrophil
effector
functions
compared
wild-type
iNeutrophils.
also
shift
their
metabolism
following
stimulation
fungal
β-glucan
pentose
phosphate
pathway
(PPP),
similar
Furthermore,
integrin
CD18
attenuates
ability
GATA1-KO
kill
A.
fumigatus
but
is
not
necessary
metabolic
shift.
Collectively,
these
findings
support
as
robust
immunity
identified
specific
roles
response.
Language: Английский
Influence of cell bioenergetics on host-pathogen interaction in the lung
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 3, 2025
Pulmonary
diseases,
arising
from
infections
caused
by
bacteria,
fungi,
and
viruses,
or
stemming
underlying
genetic
factors
are
one
of
the
leading
causes
mortality
in
humans,
accounting
for
millions
deaths
every
year.
At
onset
pulmonary
crucial
roles
played
phagocytic
immune
cells,
particularly
tissue-resident
macrophages,
regulating
response
at
mucosal
barrier.
Recent
strides
have
illuminated
pivotal
role
host
bioenergetics
modulated
metabolites
derived
both
pathogens
hosts
influencing
pathophysiology
major
organs.
Their
influence
extends
to
processes
such
as
infiltration
activation
polarization
phenomenon.
Furthermore,
host-derived
metabolites,
itaconate,
contribute
promotion
anti-inflammatory
responses,
thereby
preventing
immunopathology
facilitating
preservation
niches
thrive
long-term.
This
review
explores
recent
advancements
field
immunometabolism,
with
a
particular
emphasis
on
intricacies
disease
progression
bacteria
P.
aeruginosa,
M.
tuberculosis
S.
aureus
fungi
like
C.
albicans.
Language: Английский
Metabolic homeostasis in fungal infections from the perspective of pathogens, immune cells, and whole-body systems
Microbiology and Molecular Biology Reviews,
Journal Year:
2024,
Volume and Issue:
88(3)
Published: Sept. 4, 2024
SUMMARY
The
ability
to
overcome
metabolic
stress
is
a
major
determinant
of
outcomes
during
infections.
Pathogens
face
nutrient
and
oxygen
deprivation
in
host
niches
their
encounter
with
immune
cells.
Immune
cells
require
adaptations
for
producing
antimicrobial
compounds
mounting
antifungal
inflammation.
Infection
also
triggers
systemic
changes
organ
metabolism
energy
expenditure
that
range
from
an
enhanced
produce
robust
response
reduced
as
infection
progresses,
which
coincides
dysfunction.
Competition
nutrients
between
hosts
pathogens
means
successful
survival
recovery
balance
elimination
the
pathogen
by
systems
(resistance),
doing
so
minimal
damage
tissues
organs
(tolerance).
Here,
we
discuss
our
current
knowledge
pathogen,
cell
fungal
infections,
impact
disorders,
such
obesity
diabetes.
We
put
forward
idea
that,
while
use
regulation
proliferation
responses
(i.e.,
resistance)
has
been
growing
over
years,
need
study
mechanisms
control
tolerance
pathogens.
A
comprehensive
understanding
how
resistance
interventions
may
provide
insights
into
therapeutic
strategies
could
be
used
adjunctly
drugs
improve
patient
outcomes.
Language: Английский
GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 11, 2024
Abstract
Neutrophils
are
critical
for
host
defense
against
fungi.
However,
the
short
life
span
and
lack
of
genetic
tractability
primary
human
neutrophils
has
limited
in
vitro
analysis
neutrophil-fungal
interactions.
Human
induced
pluripotent
stem
cell
(iPSC)-derived
(iNeutrophils)
a
genetically
tractable
alternative
to
neutrophils.
Here,
we
show
that
deletion
transcription
factor
GATA1
from
iPSCs
results
iNeutrophils
with
improved
antifungal
activity
Aspergillus
fumigatus
.
knockout
(KO)
have
increased
maturation,
pattern
recognition
receptor
expression
more
readily
execute
neutrophil
effector
functions
compared
wild-type
iNeutrophils.
also
shift
their
metabolism
following
stimulation
fungal
β-glucan,
including
an
upregulation
pentose
phosphate
pathway
(PPP),
similar
Furthermore,
integrin
CD18
attenuates
ability
GATA1-KO
kill
A.
but
is
not
necessary
PPP.
Collectively,
these
findings
support
as
robust
system
study
immunity
identified
specific
roles
response.
Author
Summary
important
first
responders
infections,
understanding
essential
better
elucidating
disease
dynamics.
Primary
lived
do
permit
manipulation,
limiting
use
interactions
analyses.
In
this
report
GATA1-deficient
generate
mature
than
display
pathogen
We
receptors
cells
at
levels
comparable
Deletion
blocks
control
growth
,
demonstrating
role
iNeutrophil
activity.
model
immunity.
Language: Английский
The nasal mycobiome of individuals with allergic rhinitis and asthma differs from that of healthy controls in composition, structure and function
Frontiers in Microbiology,
Journal Year:
2024,
Volume and Issue:
15
Published: Dec. 17, 2024
Allergic
rhinitis
(AR)
and
asthma
(AS)
are
two
of
the
most
common
chronic
respiratory
diseases
a
major
public
health
concern.
Multiple
studies
have
demonstrated
role
nasal
bacteriome
in
AR
AS,
but
little
is
known
about
airway
mycobiome
its
potential
association
to
inflammatory
diseases.
Here
we
used
internal
transcriber
spacers
(ITS)
1
2
high-throughput
sequencing
characterize
339
individuals
with
AR,
(ARAS),
AS
healthy
controls
(CT).
Seven
ten
14
abundant
fungal
genera
(
Malassezia,
Alternaria,
Cladosporium,
Penicillium,
Wallemia,
Rhodotorula,
Sporobolomyces,
Naganishia,
Vishniacozyma
,
nd
Filobasidium
)
cavity
differed
significantly
p
≤
0.049)
between
or
ARAS,
CT.
However,
none
same
varied
three
disease
groups.
The
mycobiomes
ARAS
patients
showed
highest
intra-group
diversity,
while
CT
lowest.
Alpha-diversity
indices
microbial
richness
evenness
only
0.024)
CT,
all
groups
significant
differences
0.0004)
structure
(i.e.,
beta-diversity
indices)
when
compared
samples.
Thirty
metabolic
pathways
(PICRUSt2)
were
differentially
(Wald’s
test)
patients,
them
associated
5-aminoimidazole
ribonucleotide
(AIR)
biosynthesis
over
(log2
Fold
Change
>0.75)
group.
AIR
has
been
pathogenesis
plants.
Spiec-Easi
networks
among
groups,
more
similar
interactions
their
members
than
those
mycobiome;
this
suggests
allergic
may
disrupt
connectivity
cavity.
This
study
contributes
valuable
data
results
understand
relationships
allergy-related
conditions.
It
demonstrates
for
first
time
that
mycobiota
varies
during
(with
without
comorbid
asthma)
reveals
specific
taxa,
relate
disease.
Language: Английский