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Previous issue date: 2015-04-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / A leishmaniose visceral (LV) ? uma doen?a end?mica em muitos pa?ses,
incluindo o Brasil. O protozo?rio Leishmania infantum ? o agente etiol?gico da
LV, sendo transmitido pela picada das f?meas dos flebotom?neos, durante o
repasto sangu?neo. A maioria dos indiv?duos quando expostos ao parasita n?o
desenvolvem a doen?a, pois apresentam um predom?nio da resposta celular
Th1. Aqueles que desenvolvem doen?a, apresentam sinais como febre, perda de
peso, hepatoesplenomegalia e um comprometimento da resposta imune celular,
espec?fica a ant?genos de Leishmania. N?s avaliamos se essa anergia,
observada durante a doen?a ativa, poderia estar associada com altera??es nas
mol?culas coestimulat?rias de linf?citos T ou em seus ligantes em mon?citos
CD14+. H? aumento na porcentagem de CTLA-4 em linf?citos T CD4+ (p=0,001)
e ICOS em linf?citos T CD4+ e CD8+ (p=0,002 para CD4+ e p=0,003 para
CD8+) ap?s est?mulo por ant?geno sol?vel de Leishmania (SLA) na LV
sintom?tica, e que h? maior porcentagem dessas mol?culas ex vivo, quando
comparados indiv?duos sintom?ticos aos recuperados (p=0,04 para CTLA-4 em
CD4+, e p=0,001 para ICOS em CD4+ e p=0,026 para CD8+). Al?m disso,
encontramos uma maior express?o dos genes CTLA-4, OX-40 e ICOS, durante
a LV ativa. As mol?culas CD40, CD80, CD86, HLA-DR e ICOSL, n?o sofrem
altera??o durante a doen?a. H? produ??o de IFN-? por c?lulas de sangue
perif?rico, ap?s est?mulo por SLA, em indiv?duos sintom?ticos; no entanto, h?
diminui??o na raz?o entre IFN-?/IL-10, com aumento desta ap?s a cura. A
observa??o do comprometimento de algumas vias de mol?culas coestimulat?rias
poderia diminuir a capacidade microbicida dos fag?citos, durante a leishmaniose
visceral sintom?tica, podendo facilitar a sobreviv?ncia e a prolifera??o do
parasita. / Visceral leishmaniasis (VL) is endemic in many countries, including Brazil. The
protozoan Leishmania infantum, is the etiological agent of VL, and is transmitted
by the bite of female sandflies during the blood meal. The majority of subjects
when exposed to the parasite do not develop the disease, because of
development of Th1 cellular responses. Those who have develop signs of VL
such as fever, weight loss, hepatosplenomegaly, have impairment of the cellular
immune response, specific to the Leishmania antigens. We evaluated whether
the specififc anergy during symptomatic VL, may be associated with changes in T
cells costimulatory molecules or their ligands in CD14+ monocytes. There is an
increase in CTLA-4 porcentage on CD4+ T lymphocytes (p=0.001) and ICOS on
CD4+ and CD8+ T cells (p=0.002 to CD4+ and p=0.003 to CD8+), after
stimulation by soluble Leishmania antigen (SLA) during active visceral
leishmaniasis, and that there is a higher percentage of these molecules ex vivo,
when comparing symptomatic to recovered individuals (p=0.04 to CTLA-4 in
CD4+, and p=0.001 to ICOS in CD4+ and p=0.026 to CD8+). Moreover, we
found a high gene expression of CTLA-4, OX-40 and ICOS during active VL.
CD40, CD80, CD86, HLA-DR and ICOSL molecules do not suffer changes during
disease. There is IFN-? production by the peripheral blood cells, after SLA
stimulation, by peripheral blood cells in symptomatic subjects; however, there is a
decrease of the ratio IFN-?/IL-10, which is reversed after clinical recovery. The
impairment of some costimulatory molecules pathways during symptomatic VL
could inhibit the ability of phagocytes to kill Leishmania and could facilitate their
survival and the proliferation inside macrophages.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/19910 |
| Date | 27 April 2015 |
| Creators | Rodrigues Neto, Jo?o Firmino |
| Contributors | 15603016434, http://lattes.cnpq.br/7120263570947836, Salha, Daniella Regina Arantes Martins, 91622301404, http://lattes.cnpq.br/3695151190501921, Lacerda, H?nio Godeiro, 79105017491, http://lattes.cnpq.br/5385381875845273, Carvalho, Lucas Pedreira de, 88323145504, http://lattes.cnpq.br/7308383096084856, Moreira, Paula Viviane de Souza Queiroz, 02498237488, Jer?nimo, Selma Maria Bezerra |
| Publisher | Universidade Federal do Rio Grande do Norte, PROGRAMA DE P?S-GRADUA??O EM BIOQU?MICA, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| 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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