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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
"blindness"
symptom
aniridia
canavan disease
coats disease
cohen syndrome
congenital toxoplasmosis
cystinuria
dracunculiasis
fabry disease
gm1 gangliosidosis
junctional epidermolysis bullosa
kallmann syndrome
lamellar ichthyosis
neonatal adrenoleukodystrophy
oculocutaneous albinism
x-linked adrenoleukodystrophy
This symptom has already been validated