mSphere of Influence: Complement activity beyond systemic circulation—implications in the context of infections
mSphere,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 7, 2025
ABSTRACT
Jigar
V.
Desai
works
in
the
field
of
immunology,
studying
mucosal
and
systemic
complement
systems
their
roles
regulating
immune
response.
In
this
mSphere
Influence
article,
he
reflects
on
how
papers
by
Kemper,
Kulkarni,
Kasper
laboratories
made
an
impact
his
ongoing
work
investigating
cell-intrinsic
extrinsic
regulation
its
impacts
immunity.
Language: Английский
Complement and fungal diseases
Journal of Allergy and Clinical Immunology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 1, 2025
Language: Английский
The C3-C3aR axis modulates trained immunity in alveolar macrophages
Published: March 31, 2025
Complement
protein
C3
is
crucial
for
immune
responses
in
mucosal
sites
such
as
the
lung,
where
it
aids
microbe
elimination
and
enhances
inflammation.
While
trained
immunity
–
enhanced
secondary
of
innate
cells
after
prior
exposure
well-studied,
role
complement
system
remains
unclear.
We
investigated
found
that
vivo
,
wild-type
mice
showed
significantly
elevated
pro-inflammatory
cytokines
increased
C3a
levels
upon
a
second
stimulus,
whereas
C3-deficient
exhibited
blunted
cytokine
response
heightened
evidence
lung
injury.
Ex
alveolar
macrophages
(AMs)
displayed
reduced
chemokine
output
training,
which
was
restored
by
exogenous
but
not
C3a.
Inhibiting
C3aR,
both
pharmacologically
with
genetic
C3aR
knockout,
prevented
this
restoration,
indicating
necessity
engagement.
Mechanistically,
WT
AMs
demonstrated
glycolytic
activity
compared
to
defect
corrected
C3aR-dependent
manner.
These
findings
reveal
modulates
through
signaling,
affecting
production
metabolic
reprogramming,
highlight
novel
immunity.
Language: Английский
The C3-C3aR axis modulates trained immunity in alveolar macrophages
Published: March 31, 2025
Complement
protein
C3
is
crucial
for
immune
responses
in
mucosal
sites
such
as
the
lung,
where
it
aids
microbe
elimination
and
enhances
inflammation.
While
trained
immunity
–
enhanced
secondary
of
innate
cells
after
prior
exposure
well-studied,
role
complement
system
remains
unclear.
We
investigated
found
that
vivo
,
wild-type
mice
showed
significantly
elevated
pro-inflammatory
cytokines
increased
C3a
levels
upon
a
second
stimulus,
whereas
C3-deficient
exhibited
blunted
cytokine
response
heightened
evidence
lung
injury.
Ex
alveolar
macrophages
(AMs)
displayed
reduced
chemokine
output
training,
which
was
restored
by
exogenous
but
not
C3a.
Inhibiting
C3aR,
both
pharmacologically
with
genetic
C3aR
knockout,
prevented
this
restoration,
indicating
necessity
engagement.
Mechanistically,
WT
AMs
demonstrated
glycolytic
activity
compared
to
defect
corrected
C3aR-dependent
manner.
These
findings
reveal
modulates
through
signaling,
affecting
production
metabolic
reprogramming,
highlight
novel
immunity.
Language: Английский
The Establishment of Complement System Is from Gene Duplication and Domain Shuffling
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(15), P. 8119 - 8119
Published: July 25, 2024
The
mammalian
complement
system
constitutes
a
highly
sophisticated
body
defense
machinery.
evolutionary
origin
of
the
can
be
traced
to
Coelenterata
as
presence
central
component
C3
and
two
activation
proteases
BF
MASP.
In
present
study,
main
components
were
screened
analyzed
from
genomes
different
species
in
metazoan
subphyla/phyla.
C1q
with
classical
domains
Annelida,
ficolin
MBL
Urochordata.
C1r
C1s
are
only
found
Chondrichthyes
even
higher
species,
MASP
is
Coelenterata.
tree,
Vertebrates
close
MASP1/2/3
Deuterostomia
Coelenterata,
MASP-like
protease
(MASPL)
Arthropoda,
Mollusca,
Annelida.
C2,
BF,
DF
Porifera,
respectively.
There
no
clear
C2
branches
tree.
C4
C5
species.
three
C3,
C4,
C6-like
(C6L)
C8
Urochordata,
C7-like
(C7L)
Cephalochordara.
C6L,
C7L,
Urochordata
Cephalochordara
provide
structural
conditions
for
formation
Vertebrate
MAC
components.
findings
unveil
principles
insight
into
its
sophistication.
Language: Английский
The C3-C3aR axis modulates trained immunity in alveolar macrophages
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 3, 2024
ABSTRACT
Complement
protein
C3
is
crucial
for
immune
responses
in
mucosal
sites
such
as
the
lung,
where
it
aids
microbe
elimination
and
enhances
inflammation.
While
trained
immunity
–
enhanced
secondary
of
innate
cells
after
prior
exposure
well-studied,
role
complement
system
remains
unclear.
We
investigated
found
that
vivo
,
wild-type
mice
showed
significantly
elevated
pro-inflammatory
cytokines
increased
C3a
levels
upon
a
second
stimulus,
whereas
C3-deficient
exhibited
blunted
cytokine
response
heightened
evidence
lung
injury.
Ex
alveolar
macrophages
(AMs)
displayed
reduced
chemokine
output
training,
which
was
restored
by
exogenous
but
not
C3a.
Inhibiting
C3aR,
both
pharmacologically
with
genetic
C3aR
knockout,
prevented
this
restoration,
indicating
necessity
engagement.
Mechanistically,
WT
AMs
demonstrated
glycolytic
activity
compared
to
defect
corrected
C3aR-dependent
manner.
These
findings
reveal
modulates
through
signaling,
affecting
production
metabolic
reprogramming,
highlight
novel
immunity.
Language: Английский
Impaired complement regulation drives chronic lung allograft dysfunction after lung transplantation.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 18, 2024
ABSTRACT
A
greater
understanding
of
chronic
lung
allograft
dysfunction
(CLAD)
pathobiology,
the
primary
cause
mortality
after
transplantation,
is
needed
to
improve
outcomes.
The
complement
system
links
innate
adaptive
immune
responses
and
activated
early
post-lung
transplantation
form
C3
convertase,
a
critical
enzyme
that
cleaves
central
component
C3.
We
hypothesized
LTx
recipients
with
genetic
predisposition
enhanced
activation
have
worse
CLAD-free
survival
mediated
through
increased
alloimmunity.
interrogated
known
functional
polymorphism
(C3R102G)
increases
impaired
convertase
inactivation
in
two
independent
recipient
cohorts.
C3R102G,
identified
at
least
one
out
three
recipients,
was
associated
survival,
particularly
subset
who
developed
donor-specific
antibodies
(DSA).
In
mouse
orthotopic
model,
regulation
resulted
more
severe
obstructive
airway
lesions
when
compared
wildtype
controls,
despite
only
moderate
differences
graft-infiltrating
effector
T
cells.
Impaired
promoted
intragraft
accumulation
memory
B
cells
antibody-secreting
cells,
resulting
DSA
levels.
summary,
cell
survival.
BRIEF
SUMMARY
Lung
transplant
genetically
predisposed
demonstrate
rejection-free
This
phenotype
cell-activation
antibodies.
Language: Английский