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Complex adaptive immunity to enteric fevers in humans: lessons learned and the path forward.
[typhoid]
Salmonella
enterica
serovar
Typhi
(
S
.
Typhi
)
,
the
causative
agent
of
typhoid
fever
,
and
S
.
Paratyphi
A
and
B
,
causative
agents
of
paratyphoid
fever
,
are
major
public
health
threats
throughout
the
world
.
Although
two
licensed
typhoid
vaccines
are
currently
available
,
they
are
only
moderately
protective
and
immunogenic
necessitating
the
development
of
novel
vaccines
.
A
major
obstacle
in
the
development
of
improved
typhoid
,
as
well
as
paratyphoid
vaccines
is
the
lack
of
known
immunological
correlates
of
protection
in
humans
.
Considerable
progress
has
been
made
in
recent
years
in
understanding
the
complex
adaptive
host
responses
against
S
.
Typhi
.
Although
the
induction
of
S
.
Typhi-
specific
antibodies
(
including
their
functional
properties
)
and
memory
B
cells
,
as
well
as
their
cross-reactivity
with
S
.
Paratyphi
A
and
S
.
Paratyphi
B
has
been
shown
,
the
role
of
humoral
immunity
in
protection
remains
undefined
.
Cell
mediated
immunity
(
CMI
)
is
likely
to
play
a
dominant
role
in
protection
against
enteric
fever
pathogens
.
Detailed
measurements
of
CMI
performed
in
volunteers
immunized
with
attenuated
strains
of
S
.
Typhi
have
shown
,
among
others
,
the
induction
of
lymphoproliferation
,
multifunctional
type
1
cytokine
production
,
and
CD
8
(
+
)
cytotoxic
T
-
cell
responses
.
In
addition
to
systemic
responses
,
the
local
microenvironment
of
the
gut
is
likely
to
be
of
paramount
importance
in
protection
from
these
infections
.
In
this
review
,
we
will
critically
assess
current
knowledge
regarding
the
role
of
CMI
and
humoral
immunity
following
natural
S
.
Typhi
and
S
.
Paratyphi
infections
,
experimental
challenge
,
and
immunization
in
humans
.
We
will
also
address
recent
advances
regarding
cross-talk
between
the
host
's
gut
microbiota
and
immunization
with
attenuated
S
.
Typhi
,
mechanisms
of
systemic
immune
responses
,
and
the
homing
potential
of
S
.
Typhi-
specific
B-
and
T
-
cells
to
the
gut
and
other
tissues
.
Diseases
Validation
Diseases presenting
"fever"
symptom
22q11.2 deletion syndrome
acute rheumatic fever
alexander disease
allergic bronchopulmonary aspergillosis
canavan disease
carcinoma of the gallbladder
child syndrome
congenital toxoplasmosis
cushing syndrome
cystinuria
dracunculiasis
erdheim-chester disease
esophageal adenocarcinoma
esophageal carcinoma
familial mediterranean fever
focal myositis
hodgkin lymphoma, classical
lamellar ichthyosis
legionellosis
locked-in syndrome
malignant atrophic papulosis
neonatal adrenoleukodystrophy
neuralgic amyotrophy
oculocutaneous albinism
papillon-lefèvre syndrome
pyomyositis
pyruvate dehydrogenase deficiency
scrub typhus
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
typhoid
waldenström macroglobulinemia
wolf-hirschhorn syndrome
This symptom has already been validated