Chemical Biology & Drug Design,
Год журнала:
2024,
Номер
104(6)
Опубликована: Дек. 1, 2024
ABSTRACT
The
immune
system
is
essential
for
the
defense
against
infections
and
critically
implicated
in
various
disorders,
including
immunodeficiency,
autoimmunity,
inflammation
cancer.
current
study
includes
a
new
design
of
palmitoylated
derivatives
thioglycolic
acids
(PTGAs)
capable
triggering
innate
responses.
series
were
accessible
through
three‐step
synthetic
route,
N
‐palmitoylation,
Claisen–Schmidt
condensation
thia‐Michael
addition.
Their
structures
elucidated
using
different
1D
2D
NMR
spectroscopic
techniques
their
purity
was
confirmed
by
elemental
analysis.
most
active
PTGAs
induced
12–26‐fold
increase
expression
TNF‐α
IL‐1β
mRNA
triggered
marked
release
NO
isolated
macrophages.
These
levels
comparable
to
responses
elicited
heat‐killed
E.
coli
S.
aureus
.
position
palmitamide
chain
aryl
substitution
had
significant
effect
on
release.
Simulations
molecular
dockings
showed
that
PTGA
occupy
same
TLR2/TLR6
heterodimer
binding
site
microbial
diacylated
lipoproteins.
immunomodulators
may
have
profound
impact
clinical
disorders
associated
with
dysfunctional
immunity.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 22, 2024
Abstract
The
nasal,
oropharyngeal,
and
bronchial
mucosa
are
primary
contact
points
for
airborne
pathogens
like
Mycobacterium
tuberculosis
(Mtb),
SARS-CoV-2,
influenza
virus.
While
mucosal
surfaces
can
function
as
both
entry
barriers
to
infection,
mucosa-associated
lymphoid
tissues
(MALT)
facilitate
early
immune
responses
antigens.
MALT
contains
a
variety
of
specialized
epithelial
cells,
including
rare
cell
type
called
microfold
(M
cell)
that
functions
transport
apical
antigens
basolateral
antigen-presenting
crucial
step
in
the
initiation
immunity.
M
cells
have
been
extensively
characterized
gastrointestinal
(GI)
tract
murine
human
models.
However,
precise
development
airway
is
unknown.
Here,
using
single-nucleus
RNA
sequencing
(snRNA-seq),
we
generated
an
atlas
from
adenoid
identified
16
unique
types
representing
basal,
club,
hillock,
hematopoietic
lineages,
defined
their
developmental
trajectories,
determined
cell-cell
relationships.
Using
trajectory
analysis,
found
develop
progenitor
club
express
gene
signature
distinct
intestinal
cells.
Surprisingly,
also
heretofore
unknown
demonstrating
robust
interferon-stimulated
signature.
Our
analysis
enhances
our
understanding
role
This
work
provides
resource
interactions
with
platform
vaccines.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 18, 2024
ABSTRACT
Our
knowledge
about
the
meningeal
immune
system
has
recently
burgeoned,
particularly
our
understanding
of
how
innate
and
adaptive
effector
cells
are
mobilized
to
meet
brain
challenges.
However,
information
on
immunocytes
guard
homeostasis
in
healthy
individuals
remains
sparse.
This
study
highlights
heterogeneous
polyfunctional
regulatory-T
(Treg)
cell
compartment
meninges.
A
Treg
subtype
specialized
controlling
Th1-cell
responses
another
known
control
B-cell
follicles
were
substantial
components
this
compartment,
foretelling
that
punctual
Treg-cell
ablation
rapidly
unleashed
interferon-gamma
production
by
lymphocytes,
unlocked
their
access
parenchyma,
altered
profiles.
Distally,
hippocampus
assumed
a
reactive
state,
with
morphological
transcriptional
changes
multiple
glial-cell
types;
within
dentate
gyrus,
neural
stem
showed
exacerbated
death
desisted
from
further
differentiation,
associated
inhibition
spatial-reference
memory.
Thus,
multifaceted
bulwark
at
steady-state.
One
sentence
summary
distinct
population
regulatory
T
murine
meninges
safeguards
keeping
local
interferon-γ-producing
lymphocytes
check,
thereby
preventing
invasion
activation
hippocampal
glial
cells,
memory
decay.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 12, 2024
Abstract
Licensed
parenteral
influenza
vaccines
induce
systemic
antibody
responses
and
alleviate
disease
severity
but
do
not
efficiently
prevent
viral
entry
transmission
due
to
the
lack
of
local
mucosal
immune
responses.
Here,
we
describe
intranasal
booster
strategy
with
unadjuvanted
recombinant
hemagglutinin
(HA)
following
initial
mRNA-LNP
vaccination,
Prime
HA.
This
regimen
establishes
highly
protective
HA-specific
memory
in
respiratory
tract.
Intranasal
HA
boosters
provided
significantly
reduced
replication
compared
both
young
old
mice.
Correlation
analysis
revealed
that
slightly
increased
levels
nasal
IgA
are
associated
a
burden
upper
boosting
an
antigenically
distinct
H1
conferred
sterilizing
immunity
against
heterologous
H1N1
virus
challenge.
Additionally,
heterosubtypic
H5
elicited
cross-reactive
humoral
Our
work
illustrates
potential
protein
as
needle-
adjuvant-free
infection
from
A
viruses.
One
Sentence
Summary
Adjuvant-free
induces
infection.
Advances in chemical and materials engineering book series,
Год журнала:
2024,
Номер
unknown, С. 267 - 286
Опубликована: Окт. 22, 2024
The
development
of
potent
and
efficacious
vaccinations
is
an
essential
task
for
preventing
infectious
diseases
reducing
the
global
burden
disease.
Nanotechnology
offers
innovative
strategies
to
design
deliver
vaccines
with
improved
immunogenicity,
stability,
other
properties.
Nanomaterials
play
multifaceted
roles
in
immunomodulation.
delivery
antigens
via
nanomaterials
such
as
carbon-based,
lipid,
polymeric,
fiber-based,
metallic,
newer
technologies
has
a
certain
edge
enhanced
bioavailability,
controlled
release
profile,
even
enabling
processes
single,
multitargeting,
imaging.
This
chapter
highlights
advancements
history
nanomaterials,
including
their
development,
structures,
methods
preparation,
mechanisms
advantages
carriers,
excipients,
or
tool
improving
current
vaccination
methods.
In
addition
above,
this
also
deals
benefits
over
traditional
vaccine
challenges
faced
development.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 3, 2024
Abstract
The
success
of
the
live
attenuated
Yellow
Fever
vaccine
(YF17D)
that
elicits
immunity
lasting
over
thirty
years
has
made
it
a
widely
used
model
to
understand
generation
durable
protection.
We
compare
early
single-cell
level
transcriptional
response
in
mice
YF17D
and
an
adjuvanted-inactivated,
but
less
effective
version
(InYF).
Within
first
week,
we
identify
70
kinetic
patterns
45
cellular
clusters,
majority
which
discriminate
between
two
formulations,
some
tissue
sex-specific
manner.
Intriguingly,
differential
transcripts
fall
into
categories,
one
whose
association
with
or
InYF
is
maintained
even
when
decoupled
from
their
cell-type
expression
other
where
such
cell-plus-gene
pairing
critical
maintain
marker
status.
demonstrate
applications
this
resource,
by
identifying
B
cells
varied
interferon
antigen
responsiveness
relation
each
vaccine.
This
high-resolution
dataset
amenable
further
biomarker
discovery
hypothesis
generation.
Chemical Biology & Drug Design,
Год журнала:
2024,
Номер
104(6)
Опубликована: Дек. 1, 2024
ABSTRACT
The
immune
system
is
essential
for
the
defense
against
infections
and
critically
implicated
in
various
disorders,
including
immunodeficiency,
autoimmunity,
inflammation
cancer.
current
study
includes
a
new
design
of
palmitoylated
derivatives
thioglycolic
acids
(PTGAs)
capable
triggering
innate
responses.
series
were
accessible
through
three‐step
synthetic
route,
N
‐palmitoylation,
Claisen–Schmidt
condensation
thia‐Michael
addition.
Their
structures
elucidated
using
different
1D
2D
NMR
spectroscopic
techniques
their
purity
was
confirmed
by
elemental
analysis.
most
active
PTGAs
induced
12–26‐fold
increase
expression
TNF‐α
IL‐1β
mRNA
triggered
marked
release
NO
isolated
macrophages.
These
levels
comparable
to
responses
elicited
heat‐killed
E.
coli
S.
aureus
.
position
palmitamide
chain
aryl
substitution
had
significant
effect
on
release.
Simulations
molecular
dockings
showed
that
PTGA
occupy
same
TLR2/TLR6
heterodimer
binding
site
microbial
diacylated
lipoproteins.
immunomodulators
may
have
profound
impact
clinical
disorders
associated
with
dysfunctional
immunity.
