Identificação e caracterização das células imunorregulatórias que participam da tolerância oral bystander na inibição da progressão da lesão inflamatória em camundongos infectados com Leishmania amazonensis

• Autor(a) principal: Benfica, Juliana do Outeiro Santos
• Data de Publicação: 2015
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/14342
• topic: Oral tolerance; Bystander suppression; Leishmania amazonensis; Regulatory T cells; Tolerogenic dendritic cells; Tolerância oral; Supressão bystander; Leishmania amazonensis; Células T regulatórias; Células dendríticas tolerogênicas; Tolerância imunológica; Leishmaniose; Leishmania amazonensis; Células T; Células dendríticas; Comunicação celular; Camundongos como animais de laboratório; CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA

The Oral Tolerance (OT) is a physiological mechanism of systemic non-inflammatory activity to a previously ingested immunogen and mediated by regulatory cells. In Bystander suppression by OT, responses to a second immunogen are regulated when it is presented along with the immunogen for which tolerance was previously established. Two strains of mice with extreme phenotypes of susceptibility (TS) and resistance (TR) to OT were developed by bidirectional genetic selection. The TS strain has a regulatory profile and, when infected with Leishmania amazonensis, develops a reduced lesion; while the TR strain develops an exacerbate lesion due to their inflammatory profile. TR mice subjected to bystander oral tolerance, that is, tolerized with ovalbumin (2mg OVA), immunized with OVA and, simultaneously infected, develop a reduced lesion. The aim of this study was to evaluate the participation of immunoregulatory cells (regulatory T lymphocytes - Tregs - and tolerogenic dendritic cells) in reducing inflammatory lesions in animals treated with oral tolerance and infected with L. amazonensis. TR mice subjected to bystander oral tolerance have increased Treg cells at the site of infection associated with reduced inflammatory lesion. Adoptive transfer of Tregs from tolerized mice (2mg OVA) to infected and immunized (OVA) TR individuals mimics the effect of bystander oral tolerance, decreasing the inflammatory lesion, suggesting the involvement of Treg cells in the bystander suppression. In addition, tolerogenic dendritic cells (DCs) were transferred from the mesenteric lymph nodes of tolerized TR or TS individuals to infected TR mice. The development of the inflammatory lesion and the percentage of Tregs (CD4+ CD25+ Foxp3+) in the infected animals were evaluated. The development of the infection was lower in TR mice that received tolerogenic DCs (from both TR as TS tolerized), compared to the ones solely infected, and being similar to the induced and infected group (bystander oral tolerance), suggesting the participation of Treg cells in bystander suppression. The tolerogenic DCs transfer also increased the percentage of Tregs in infected TR mice. Our results allow to infer that the tolerogenic DCs, possibly inducing the differentiation of Treg cells, participate in the reduction of inflammatory lesions in animals infected with L. amazonensis, as one of the mechanisms of bystander oral tolerance.