Journal of Clinical Investigation,
Год журнала:
2023,
Номер
133(13)
Опубликована: Май 18, 2023
Heterogeneity
in
human
immune
responses
is
difficult
to
model
standard
laboratory
mice.
To
understand
how
host
variation
affects
BCG-induced
immunity
against
Mycobacterium
tuberculosis,
we
studied
24
unique
Collaborative
Cross
(CC)
mouse
strains,
which
differ
primarily
the
genes
and
alleles
they
inherit
from
founder
strains.
The
CC
strains
were
vaccinated
with
or
without
BCG,
then
challenged
aerosolized
M.
tuberculosis.
As
BCG
protects
only
half
of
tested,
conclude
that
genetics
has
a
major
influence
on
tuberculosis
infection,
making
it
an
important
barrier
vaccine-mediated
protection.
Importantly,
efficacy
dissociable
inherent
susceptibility
TB.
T
cell
was
extensively
characterized
identify
components
associated
protection
stimulated
by
recalled
after
Mtb
infection.
Although
considerable
diversity
observed,
little
impact
composition
cells
lung
Instead,
variability
largely
shaped
genetics.
BCG-elicited
TB
correlated
changes
function.
Thus,
mice
can
be
used
define
correlates
vaccine
strategies
protect
larger
fraction
genetically
diverse
individuals
instead
optimizing
for
single
genotype.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Март 7, 2022
The
defining
pathology
of
tuberculosis
is
the
granuloma,
an
organized
structure
derived
from
host
immune
cells
that
surrounds
infecting
Mycobacterium
.
As
location
much
bacteria
in
infected
host,
granuloma
a
central
point
interaction
between
and
bacterium.
This
review
describes
signals
cellular
reprogramming
drive
formation.
Further,
as
host-bacterial
interactions,
shapes
disease
outcome
by
altering
responses
bacterial
susceptibility
to
antibiotic
treatment,
discussed
herein.
new
understanding
biology
signaling
behind
it
highlights
potential
for
host-directed
therapies
targeting
enhance
access
tuberculosis-specific
responses.
The Journal of Experimental Medicine,
Год журнала:
2023,
Номер
220(12)
Опубликована: Окт. 16, 2023
The
functional
role
of
CD8+
lymphocytes
in
tuberculosis
remains
poorly
understood.
We
depleted
innate
and/or
adaptive
macaques
and
showed
that
loss
all
CD8α+
cells
(using
anti-CD8α
antibody)
significantly
impaired
early
control
Mycobacterium
(Mtb)
infection,
leading
to
increased
granulomas,
lung
inflammation,
bacterial
burden.
Analysis
barcoded
Mtb
from
infected
demonstrated
depletion
allowed
establishment
lungs
dissemination
within
lymph
nodes,
while
only
T
(with
anti-CD8β
worsened
nodes.
Flow
cytometry
single-cell
RNA
sequencing
revealed
polyfunctional
cytotoxic
CD8-depleted
animals
were
unexpectedly
enriched
CD4
γδ
adopting
incomplete
signatures.
Ligand-receptor
analyses
identified
IL-15
signaling
granulomas
as
a
driver
cells.
These
data
support
are
required
for
protection
against
suggest
responses
vaccine
target.
Abstract
Breakthrough
findings
in
the
clinical
and
preclinical
development
of
tuberculosis
(TB)
vaccines
have
galvanized
field
suggest,
for
first
time
since
bacille
Calmette-Guérin
(BCG),
that
a
novel
protective
TB
vaccine
is
on
horizon.
Here
we
highlight
are
pipeline
review
basis
optimism
both
space.
We
describe
immune
signatures
could
act
as
immunological
correlates
protection
(CoP)
to
facilitate
comparison
vaccines.
Finally,
discuss
new
animal
models
expected
more
faithfully
model
pathology
complex
responses
observed
human
populations.
The Journal of Experimental Medicine,
Год журнала:
2023,
Номер
220(6)
Опубликована: Март 15, 2023
The
hallmark
of
tuberculosis
(TB)
is
the
formation
immune
cell-enriched
aggregates
called
granulomas.
While
granulomas
are
pathologically
diverse,
their
tissue-wide
heterogeneity
has
not
been
spatially
resolved
at
single-cell
level
in
human
tissues.
By
mapping
individual
cells
every
lesion
across
entire
tissue
sections,
we
report
that
addition
to
necrotizing
granulomas,
TB
lung
contains
abundant
non-necrotizing
leukocyte
surrounding
areas
tissue.
These
cellular
lesions
were
more
diverse
composition
than
and
could
be
stratified
into
four
general
classes
based
on
spatial
distribution
B
macrophages.
structures
also
correlates
with
proximity
lesions,
indicating
these
foci
distinct
reactions
adjacent
Together,
show
during
TB,
diseased
develops
a
histopathological
superstructure
comprising
least
different
types
organized
as
satellites
The Journal of Experimental Medicine,
Год журнала:
2023,
Номер
220(9)
Опубликована: Июль 22, 2023
Great
progress
has
been
made
over
the
past
half-century,
but
TB
remains
a
formidable
global
health
problem,
particularly
in
low-
and
middle-income
countries.
Understanding
mechanisms
of
pathogenesis
necessary
sufficient
conditions
for
protection
are
critical.
The
need
inexpensive
sensitive
point-of-care
diagnostic
tests
earlier
detection
infection
disease,
shorter
less-toxic
drug
regimens
drug-sensitive
-resistant
TB,
more
effective
vaccine
than
BCG
is
immense.
New
better
tools,
greater
support
international
research,
collaborations,
training
will
be
required
to
dramatically
reduce
burden
this
devastating
disease
which
still
kills
1.6
million
people
annually.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 17, 2023
Tuberculosis
(TB),
caused
by
Mycobacterium
tuberculosis
(Mtb)
and
Coronavirus
disease-2019
(COVID-19),
whose
etiologic
agent
is
severe
acute
respiratory
syndrome
coronavirus-2
(SARS-CoV-2),
are
currently
the
two
deadliest
infectious
diseases
in
humans,
which
together
have
about
more
than
11
million
deaths
worldwide
past
3
years.
TB
COVID-19
share
several
aspects
including
droplet-
aerosol-borne
transmissibility,
lungs
as
primary
target,
some
symptoms,
diagnostic
tools.
However,
these
differ
other
their
incubation
period,
immune
cells
involved,
persistence
immunopathological
response.
In
this
review,
we
highlight
similarities
differences
between
focusing
on
innate
adaptive
response
induced
after
exposure
to
Mtb
SARS-CoV-2
pathological
pathways
linking
infections.
Moreover,
provide
a
brief
overview
of
case
TB-COVID-19
co-infection
highlighting
each
individual
infection.
A
comprehensive
understanding
involved
utmost
importance
for
design
effective
therapeutic
strategies
vaccines
both
diseases.
Nature Microbiology,
Год журнала:
2023,
Номер
8(11), С. 2080 - 2092
Опубликована: Окт. 9, 2023
Abstract
Tuberculosis,
caused
by
Mycobacterium
tuberculosis
(Mtb),
is
the
most
common
cause
of
death
in
people
living
with
human
immunodeficiency
virus
(HIV).
Intra-dermal
Bacille
Calmette–Guérin
(BCG)
delivery
only
licensed
vaccine
against
tuberculosis;
however,
it
offers
little
protection
from
pulmonary
adults
and
contraindicated
HIV.
Intravenous
BCG
confers
Mtb
infection
rhesus
macaques;
we
hypothesized
that
might
prevent
simian
(SIV)-infected
macaques,
a
model
for
HIV
infection.
Here
intravenous
BCG-elicited
robust
airway
T
cell
influx
elevated
plasma
antibody
titres
both
SIV-infected
naive
animals.
Following
challenge,
all
7
vaccinated
SIV-naive
9
out
12
animals
were
protected,
without
any
culturable
bacteria
detected
tissues.
Peripheral
blood
mononuclear
responses
post-challenge
indicated
early
clearance
animals,
regardless
SIV
These
data
support
immunogenic
efficacious
Leukemia,
Год журнала:
2023,
Номер
37(3), С. 650 - 658
Опубликована: Янв. 31, 2023
Pseudo-progression
and
flare-up
phenomena
constitute
a
novel
diagnostic
challenge
in
the
follow-up
of
patients
treated
with
immune-oncology
drugs.
We
present
case
study
on
pulmonary
after
Idecabtagen
Vicleucel
(Ide-cel),
BCMA
targeting
CAR
T-cell
therapy,
used
single-cell
RNA-seq
(scRNA-seq)
to
identify
Th17.1
driven
autoimmune
mechanism
as
biological
underpinning
this
phenomenon.
By
integrating
datasets
various
lung
pathological
conditions,
we
revealed
transcriptomic
similarities
between
post
T
lesions
sarcoidosis.
Furthermore,
explored
noninvasive
PET
based
approach
showed
that
tracers
binding
CXCR4
complement
FDG
imaging
setting,
allowing
discrimination
immune-mediated
changes
true
relapse
treatment.
In
conclusion,
our
highlights
phenomenon
T,
which
may
be
misinterpreted
disease
relapse,
multiple
scRNA-seq
could
help
dilemma.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Окт. 27, 2023
Tuberculosis
(TB)
remains
a
significant
global
health
challenge,
claiming
the
lives
of
up
to
1.5
million
individuals
annually.
TB
is
caused
by
human
pathogen
