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Previous issue date: 2010-12-03 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Visceral leishmaniasis (VL) in Brazil is a disease caused by Leishmania infantum
chagasi (L.i.chagasi). The clinical evolution post-infection depends on the
vertebrate host immune response, which is genetically mediated. This study
aimed to evaluate the immune response of individuals living in endemic area for
VL in the state of the Rio Grande do Norte, considering individuals with VL under
treatment (n = 9), recovered VL <1 year post treatment (n = 10), > 10 years posttreatment
(n = 9), uninfected individuals living in endemic areas (n = 7),
individuals that lost DTH response (n=6) and asymptomatic individuals for VL
(n=9). Peripheral blood cells were evaluated in the presence and absence of
soluble Leishmania antigens (SLA) and ex vivo, to determine activation,
presence of regulatory cells and memory cells. The Leishmania parasitemia and
anti-Leishmania antibodies were determined respectively by qPCR and ELISA.
Cells from individuals with VL under treatment showed less cell activation after
stimulation with SLA for the markers CD4/CD69, CD8/CD69 and CD8/CD25
compared with VL post treatment treatment (p <0.001). Apparently uninfected
individuals have a higher cell activation than symptomatic VL (p <0.001), with the
exception of CD8/CD25 marker (p = 0.6662). On the other hand, in the ex-vivo
group, significant differences were observed for CD4/CD69, CD8/CD69 and
CD8/CD25 between the 4 groups due to increased cell activation present in cells
of individuals symptomatic LV (p <0.001). VL cells under treatment, ex vivo, have
a lower percentage of memory cells (CD4/CD45RO and CD8/CD45RO) than
individuals VL post-treatment or control group (p = <0.01). Likewise, individuals
with symptomatic VL have fewer regulatory cells when stimulated by SLA
[CD4/CD25 (p = 0.0022) and CD4/FOXP3 (p = 0.0016)] and in the ex-vivo group
(p = 0.0017). Finally, DNA isolated from recovered VL contained Leishmania
DNA, supporting the hypothesis of non-sterile clinical cure for Leishmania
infection. Recovered VL, even 10 years after treatment have high levels of
memory cells, which may be due to the presence of stimulation, either by reexposure
to Leishmania or non-sterile cure / A Leishmaniose visceral (LV) nas Am?ricas ? uma doen?a causada pela esp?cie
Leishmania infantum chagasi (L.i.chagasi). A forma cl?nica evolutiva p?s-infec??o
depende da resposta imune do hospedeiro vertebrado, que ? geneticamente
mediada. Este estudo teve como objetivo avaliar a resposta imune de indiv?duos
residentes em ?rea end?mica para LV no estado do Rio Grande do Norte,
considerando indiv?duos com LV em tratamento (n=9), indiv?duos curados de LV
< 1 ano (n=10) e > 10 anos p?s-tratamento (n=9), indiv?duos residentes em
?reas end?micas (n=7) aparentemente n?o infectados, indiv?duos que perderam
a resposta DTH (n=6) e indiv?duos assintom?ticos para LV (n=9). C?lulas de
sangue perif?rico foram avaliadas em presen?a e na aus?ncia de ant?genos
sol?veis de Leishmania (SLA) e ex-vivo, para determina??o da ativa??o, da
presen?a de c?lulas regulat?rias e de c?lulas de mem?ria. A parasitemia e
anticorpo anti-Leishmania foram determinadas, respectivamente, por qPCR e
ELISA. C?lulas oriundas de indiv?duos com LV em tratamento apresentaram
menor ativa??o celular p?s-est?mulo com SLA para os marcadores CD4/CD69,
CD8/CD69 e para CD8/CD25 quando comparado com LV p?s-tratamento
(p<0,001). Indiv?duos aparentemente n?o infectados apresentam maior ativa??o
celular que LV sintom?tico (p<0.001), com exce??o do marcador CD8/CD25
(p=0,6662). Por outro lado, na condi??o ex-vivo, diferen?as significativas foram
observadas para CD4/CD69, CD8/CD69 e CD8/CD25 devido a uma maior
ativa??o celular presente em c?lulas de indiv?duos LV sintom?ticos (p<0,001).
Indiv?duos LV sintom?ticos, ex vivo, apresentam um menor percentual de c?lulas
de mem?ria (CD4/CD45RO CD8/CD45RO) do que indiv?duos com LV p?stratamento
ou controles (p=<0.01). Da mesma forma, indiv?duos com LV
sintom?ticos apresentam uma menor quantidade de c?lulas regulat?rias quando
estimuladas por SLA [CD4/CD25 (p= 0,0022) e CD4/FOXP3 (p= 0,0016)] e na
condi??o ex-vivo (p=0.0017). Finalmente, pacientes com LV clinicamente
recuperados permaneceram com parasitemia, determinado por qPCR, dando
suporte ? hip?tese de cura cl?nica n?o est?ril para infec??o por Leishmania.
Pacientes com LV recuperado, mesmo 10 anos p?s-tratamento mant?m n?veis
elevados de c?lulas de mem?ria, que pode ser devido ? presen?a de ant?genos
de Leishmania, seja devido ? re-exposi??o ? Leishmania ou por uma prov?vel
cura n?o est?ril
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/12574 |
| Date | 03 December 2010 |
| Creators | Rodrigues Neto, Jo?o Firmino |
| Contributors | CPF:05825113568, http://lattes.cnpq.br/6998360791945569, Braz, Regina de F?tima dos Santos, CPF:00567556867, http://lattes.cnpq.br/9442000157600332, Jer?nimo, Selma Maria Bezerra, CPF:15603016434, http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785584A3&dataRevisao=null, Bacellar, Maria Olivia Amado Ramos, CPF:12436496587, http://lattes.cnpq.br/0199786420638506, Carvalho Filho, Edgar Marcelino de |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Bioqu?mica, UFRN, BR, Bioqu?mica; Biologia Molecular |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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