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https://www.arca.fiocruz.br/handle/icict/3261
ZINC/COPPER IMBALANCE REFLECTS IMMUNE DYSFUNCTION IN HUMAN LEISHMANIASIS: AN EX VIVO AND IN VITRO STUDY
Estudos de Casos e Controles
Cobre
Imunidade Celular
Imunoglobulina G
Interferon gama
Leishmania
Leishmaniose
Ativação Linfocítica
Células Th1
Células Th2
Zinco
Adolescente
Adulto
Author
Affilliation
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil.
Universidade Federal da Bahia. Instituto de Química. Salvador, BA, Brasil.
Universidade Federal do Piauí. Infectious Disease Hospital. Teresina, PI, Brasil.
Institute for Immunological Investigation. Instituto do Milênio. Sao Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Hospital Universitário Professor Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil.
Universidade Federal da Bahia. Instituto de Química. Salvador, BA, Brasil.
Universidade Federal do Piauí. Infectious Disease Hospital. Teresina, PI, Brasil.
Institute for Immunological Investigation. Instituto do Milênio. Sao Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Abstract
The process of elimination of intracellular pathogens, such as Leishmania, requires a Th1 type immune response, whereas a dominant Th2 response leads to exacerbated disease. Experimental human zinc deficiency decreases Th1 but not Th2 immune response. We investigated if zinc and copper levels differ in different clinical forms of leishmaniasis, and if these trace metals might be involved in the immune response towards the parasite.Blood was collected from 31 patients with either localized cutaneous (LCL), mucosal (ML) or visceral (VL) leishmaniasis, as well as from 25 controls from endemic and non-endemic areas. Anti-Leishmania humoral and cellular immune response were evaluated by quantifying specific plasma IgG, lymphoproliferation and cytokine production, respectively. Plasma levels of Cu and Zn were quantified by atomic absorption spectrophotometry.A significant decrease in plasma Zn was observed in all three patient groups (p < 0.01 for LCL and ML, p < 0.001 for VL), as compared to controls, but only VL (7/10) and ML (1/7) patients displayed overt Zn deficiency. Plasma Cu was increased in LCL and VL (p < 0.001) but not in ML, and was strongly correlated to anti-Leishmania IgG (Spearman r = 0.65, p = 0.0028). Cu/Zn ratios were highest in patients with deficient cellular (VL<LCL>ML) immune response. Ex vivo production of parasite-induced IFN-gamma was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.01). In vitro, increased Cu levels inhibited IFN-gamma production.1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-gamma production.
DeCS
Anticorpos AntiprotozoáriosEstudos de Casos e Controles
Cobre
Imunidade Celular
Imunoglobulina G
Interferon gama
Leishmania
Leishmaniose
Ativação Linfocítica
Células Th1
Células Th2
Zinco
Adolescente
Adulto
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