Perfil imunológico associado à susceptibilidade, resistência e cura na infecção por Leishmania ( Leishmania ) infantum
Visceral Leishmaniasis (VL) is endemic in Brazil and the northeast region had the highest incidence of the disease , despite, in the last 30 years, it has spread to all geographic regions of the country. Leishmania infantum is the m ain etiological agent...
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Formato: | doctoralThesis |
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Universidade Federal do Rio Grande do Norte
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Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/19591 |
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Resumo: | Visceral Leishmaniasis (VL) is endemic in Brazil and the northeast region had the
highest incidence
of the disease
, despite, in the last 30 years,
it
has spread
to all
geographic regions of the
country.
Leishmania infantum
is the
m
ain
etiological agent
of VL in Latin America, Europe and North Africa.
However,
not all infected individuals
develop the disease; in fact, the majority present spontaneous re
solution of infection
without
symptoms. The evaluation of the immunological profil
e has been mostly
conducted
stimulating, with
Leishmania
spp. antigen, peripheral blood mononuclear
cells
isolated from subjects with VL. These studies showed that VL patients had an
inhibition of both, lymphocyte proliferation and proinflammatory response
to
Leishmania
spp. antigen. Our study aimed to evaluate the immune response in active
LV, cured post treatment and asymptomatic infection. To reach this aim, we analyzed
immunophenotypic features related to activation, Treg and memory lymphocytes, by
flow
cytometry, as well as, evaluation of cytokine production, in
ex vivo
or in whole
blood culture. In
active
VL volunteers, a longitu
dinal study was
conducted with
reassessment at 4 and 14 months after clinical cure.
The control group included
individuals th
at live
d
in endemic region and were
either
Positive Control, consisting
of individuals with
positive anti
-
L
eishmania
spp.
serology and/or
positive
PCR
for
Leishmania
spp.
and Negative Control composed by individuals with
negative anti
-
Leishmania antibodie
s
serology and
negative
PCR
for Leishmania
. During VL, CD4
lymphocytes showed greater activation and memory profile
s
and
were
the
major
source of cytokines in culture when compared to CD8 lymphocytes
, and these were
not
Leishmania
specific. There
were
act
ivated lymphocytes during VL (CD4
+
CD69
+
:4.9%) when compared to control groups, Positive (CD4
+
CD69
+
:1.96%,
p=0.0045) and Negative (CD4
+
CD69
+
:1.35%, p=0.006), on the other hand, this was
non
-
specific activation. The lymphocyte activation profile remain
ed
el
evated even 14
months post treatmen
t. A
fter
clinical
cure
,
the activation
was
Leishmania
specific
(CD4
+
CD25
+
absence of SLA:
8.4%, and presence of SLA:
10.7% p=0.0279).
CD8
+
CD25
+
lymphocytes
were
able to produce
Leishmania
specific IFN
-
γ in both,
Positive
Controls (absence of SLA 5.2% and presence of SLA: 9.5%, p=0.0391) and
Cured 4 month (absence of SLA: 3.9%; presence of SLA: 10.7% p=0.0098). Whole
blood culture cells, of VL patients,
were
able to produce IFN
-
γ, by SLA stimulation
(absence of SLA: 28.0 pg
∕mL, and presence: 44.3 pg∕mL p=0.0020) as well as
recovered groups (absence of SLA 2.3 pg∕mL and presence of SLA 139.8 pg∕mL,
p=0.0005). However, the high level of IL
-
10 seem
ed
to inhibit pro
-
inflammatory
activity of IFN
-
γ and TNF
-
α
during symptomatic dis
ease
.
Unlike other pro
-
inflammatory cytokines, active VL group d
id
not produce
Leishmania
specific IL
-
2
(absence of SLA 2.4 pg∕mL and presence of SLA: 2.6 pg∕mL). Based on these data
we conclude that the restoration of lymphocyte activation and decreased i
n IL
-
10
Leishmania
specific production
were
related to a protective immune profile. |
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