European Journal of Immunology,
Год журнала:
2025,
Номер
55(5)
Опубликована: Май 1, 2025
The
innate
immune
system
relies
on
nucleic
acid
(NA)
sensors
to
detect
viral
infections
and
trigger
type
I
interferon
(IFN-I)
responses,
which
are
crucial
for
antiviral
defense.
NA
pattern
recognition
receptors
RNA
or
DNA
within
various
cellular
compartments,
initiating
signaling
pathways.
However,
inherited
deficiencies
in
these
sensing
mechanisms
can
result
increased
susceptibility
severe
infections.
This
review
explores
key
genetic
mutations
affecting
IFN-I
pathways
that
predispose
individuals
life-threatening
diseases,
including
herpesviruses,
respiratory
viruses,
enteroviruses,
arboviruses,
vaccine-strain
disseminated
diseases.
identification
of
monogenic
defects
afflicted
by
infections,
along
with
the
observed
incomplete
penetrance
mutations,
highlight
intricate
interplay
host's
intrinsic,
innate,
adaptive
response
invading
pathogens.
These
insights
into
molecular
basis
immunity
not
only
underscore
clinical
challenges
associated
but
also
offers
opportunity
personalized
treatment
strategies,
screening,
tailored
vaccination
protocols,
targeted
therapies.
Journal of Allergy and Clinical Immunology,
Год журнала:
2023,
Номер
151(4), С. 832 - 840
Опубликована: Фев. 24, 2023
Since
the
beginning
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)/coronavirus
disease
2019
(COVID-19)
pandemic,
global
sequencing
efforts
have
led
in
field
inborn
errors
immunity,
and
inspired
particularly
by
previous
research
on
life-threatening
influenza,
they
revealed
that
known
novel
affecting
type
I
interferon
immunity
underlie
critical
COVID-19
up
to
5%
cases.
In
addition,
neutralizing
autoantibodies
against
interferons
been
identified
20%
patients
with
who
are
older
than
80
years
fatal
cases,
a
higher
prevalence
men
individuals
70
years.
Also,
impairing
regulation
responses
RNA
degradation
found
as
causes
multisystem
inflammatory
children,
hyperinflammatory
condition
complicating
otherwise
mild
initial
SARS-CoV-2
infection
children
young
adults.
Better
understanding
these
immunologic
mechanisms
can
aid
designing
treatments
for
COVID-19,
long
COVID,
neuro-COVID.
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
221(12)
Опубликована: Ноя. 1, 2024
Arboviral
diseases
are
a
growing
global
health
concern.
Pre-existing
autoantibodies
(auto-Abs)
neutralizing
type
I
interferons
(IFNs)
can
underlie
encephalitis
due
to
West
Nile
virus
(WNV)
(∼40%
of
patients)
and
tick-borne
(TBE,
TBE
[TBEV])
(∼10%).
We
report
here
that
these
auto-Abs
also
severe
forms
rarer
arboviral
infections.
Auto-Abs
high
concentrations
IFN-α2,
IFN-β,
and/or
IFN-ω
present
in
the
single
case
Powassan
(POWV)
studied,
two
three
cases
Usutu
(USUV)
infection
most
24
Ross
River
(RRV)
disease
studied.
These
not
found
any
137
individuals
with
silent
or
mild
infections
viruses.
Thus,
IFNs
an
increasing
list
Flaviviridae
(WNV,
TBEV,
POWV,
USUV)
Togaviridae
viruses
transmitted
humans
by
mosquitos
USUV,
RRV)
ticks
(TBEV,
POWV).
The Journal of Infectious Diseases,
Год журнала:
2024,
Номер
230(2), С. e318 - e326
Опубликована: Фев. 29, 2024
Infection
with
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
can
lead
to
disease
increased
morbidity
and
mortality
among
certain
risk
groups.
The
presence
of
autoantibodies
against
type
I
interferons
(aIFN-Abs)
is
one
mechanism
that
contributes
2019
(COVID-19).
Proceedings of the National Academy of Sciences,
Год журнала:
2025,
Номер
122(12)
Опубликована: Март 18, 2025
Mycobacterium
tuberculosis
(Mtb)
primarily
infects
macrophages.
In
vitro
without
antibiotics,
wild-type
Mtb
hastens
death
of
the
macrophages,
but
processes
leading
to
rapid
cell
are
not
well
understood.
Our
earlier
work
indicated
that
Mtb-infected
mouse
macrophages
in
is
markedly
exacerbated
by
induction
interferon-β
(IFN-β)
[L.
Zhang
et
al.,
J.
Exp.
Med.
18
,
e20200887
(2021)].
Here,
we
identified
a
key
downstream
response
IFN-β
context
infection
as
massive
cis-aconitate
decarboxylase
(ACOD1),
only
its
canonical
subcellular
localization
mitochondria
also
cytosol,
where
it
bound
lysosome-stabilizing
protein
HSP70.
ACOD1’s
product,
itaconate,
protected
However,
contrasting
and
predominant
effect
high-level
ACOD1
expression
was
act
noncatalytic
manner
promote
HSP70’s
degradation,
lysosomal
membrane
permeabilization
(LMP).
Mtb-induced
macrophage
diminished
inhibitors
cysteine
proteases,
consistent
with
lysosome-mediated
death.
Neither
nor
protease
suitable
for
potential
host-directed
therapy
(HDT)
tuberculosis.
Instead,
this
directs
attention
how
acts
nonenzymatically
degradation
European Journal of Immunology,
Год журнала:
2025,
Номер
55(5)
Опубликована: Май 1, 2025
The
innate
immune
system
relies
on
nucleic
acid
(NA)
sensors
to
detect
viral
infections
and
trigger
type
I
interferon
(IFN-I)
responses,
which
are
crucial
for
antiviral
defense.
NA
pattern
recognition
receptors
RNA
or
DNA
within
various
cellular
compartments,
initiating
signaling
pathways.
However,
inherited
deficiencies
in
these
sensing
mechanisms
can
result
increased
susceptibility
severe
infections.
This
review
explores
key
genetic
mutations
affecting
IFN-I
pathways
that
predispose
individuals
life-threatening
diseases,
including
herpesviruses,
respiratory
viruses,
enteroviruses,
arboviruses,
vaccine-strain
disseminated
diseases.
identification
of
monogenic
defects
afflicted
by
infections,
along
with
the
observed
incomplete
penetrance
mutations,
highlight
intricate
interplay
host's
intrinsic,
innate,
adaptive
response
invading
pathogens.
These
insights
into
molecular
basis
immunity
not
only
underscore
clinical
challenges
associated
but
also
offers
opportunity
personalized
treatment
strategies,
screening,
tailored
vaccination
protocols,
targeted
therapies.
