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The local immune response to intraocular Toxoplasma re-challenge: less pathology and better parasite control through Treg/Th1/Th2 induction.
[congenital toxoplasmosis]
Ocular
toxoplasmosis
is
a
major
cause
of
blindness
world-
wide
.
Ocular
involvement
is
frequently
seen
following
congenital
infection
.
Many
of
these
infections
are
quiescent
but
pose
a
life-time
risk
of
reactivation
.
However
,
the
physiopathology
of
ocular
toxoplasmosis
reactivation
is
largely
unexplored
.
We
previously
developed
a
Swiss
-
Webster
outbred
mouse
model
for
congenital
toxoplasmosis
by
neonatal
injection
of
Toxoplasma
gondii
cysts
.
We
also
used
a
mouse
model
of
direct
intraocular
infection
to
show
a
deleterious
local
T
helper
17
type
response
upon
primary
infection
.
In
the
present
study
,
our
two
models
were
combined
to
study
intravitreal
re
-challenge
of
neonatally
infected
mice
,
as
an
approximate
model
of
reactivation
,
in
comparison
with
a
primary
ocular
infection
.
Using
BioPlex
proteomic
assays
in
aqueous
humour
and
reverse
transcription-
PCR
for
T
helper
cell
transcription
factors
,
we
observed
diminished
T
helper
17
type
reaction
in
reinfection
,
compared
with
primary
infection
.
In
contrast
,
T
helper
2
and
T
regulatory
responses
were
enhanced
.
Interestingly
,
this
was
also
true
for
T
helper
1
markers
such
as
IFN-γ
,
which
was
paralleled
by
better
parasite
control
.
Secretion
of
IL
-
27
,
a
central
cytokine
for
shifting
the
immune
response
from
T
helper
17
to
T
helper
1
,
was
also
greatly
enhanced
.
We
observed
a
similar
protective
immune
reaction
pattern
in
the
eye
upon
reinfection
with
the
virulent
RH
strain
,
with
the
notable
exception
of
IFN-γ
.
In
summary
,
our
results
show
that
the
balance
is
shifted
from
T
helper
17
to
a
less
pathogenic
but
more
effective
anti-parasite
Treg
/
T
helper
1
/
T
helper
2
pattern
in
a
reactivation
setting
.
Diseases
Validation
Diseases presenting
"type reaction in reinfection"
symptom
congenital toxoplasmosis
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