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Study of the correlation between the expression of the IL-17 and Foxp3 in lesion of patients with different clinical forms of American Cutaneous Leishmaniasis (ACL) caused by Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis

Grant number: 11/12564-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2011
Effective date (End): August 31, 2013
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Claudia Maria de Castro Gomes
Grantee:Izildinha Benedita de Morais
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In Brazil, despite many species of Leishmania may cause American cutaneous leishmaniasis (ACL), Leishmania (V.) braziliensis and Leishmania (L.) amazonensis are the major pathogenic species to humans. Depending of the species of the parasite and the immune response of the host, there are different clinical forms of disease, known as localized cutaneous leishmaniasis (LCL), mucocutaneous leishmaniasis (MCL), anergic diffuse cutaneous leishmaniasis (ADCL) and boderline disseminated cutaneous leishmaniasis (BDCL).In the elaboration of the immune response, the Leishmania is intracellular obligator parasite and its target cell is the macrophage. Although macrophages are major effector cells of the elimination of Leishmania, they are also able to maintain the parasite inside allowing its replication. The mechanisms involved in activation of macrophages are complex and include a network of cytokines and reactive oxygen and nitrogen species during the activation of the immune response.The T cells CD4+ CD25+ Foxp3+ (Treg) and Th17 are today, two subpopulations of CD4+ T cells widely accepted, with important roles in the induction and control of inflammatory response. These cells also play an essential role in immune homeostasis. Recent work of literature has shown a role TregFoxp3+ cell in the immune response against cutaneous leishmaniasis. In experimental infections with Leishmania major, was observed in susceptible mice, an excessive immune response suppression mediated by Th2 cells. In mice resistant to Treg control the Th1 allowing the persistence of the parasite. In ACL lesions caused by L.(V.) braziliensis and L.(L.) amazonensis was shown the accumulation of Treg cells and secretion of IL-10 and TGF-² by these cells, which favor the control of immune response mediated by effector T cells. Recent reports also showed higher expression of Foxp3+ cells in ADCL in relation to the LCL.Th17 cells are characterized by the production of IL-17, which constitutes a pro-inflammatory cytokine secreted primarily by CD4+ and CD8+. Th17 cells have shown a protective role in infection, helping to promote the elimination of the pathogen, the increased recruitment of neutrophils to the site of infection and activation of macrophages. Few studies have been conducted to evaluate the role of IL-17 in human infectious diseases. In human VL, IL-17 was associated with Th1 cytokines, related to protection. There was also a correlation between IL-17+ cells and inflammatory infiltrate in infection by L.(V.) braziliensis, high levels of cytokines related to Th17 cells were also observed in areas of tissue damage with neutrophil infiltration.Despite the immune response in leishmaniasis is well characterized, there are still many aspects that need clarification, especially with regard to the broad spectrum of human disease. Thus, this study aims to evaluate the profile of Th17 cells and regulatory T through the expression of Foxp3 and IL-17 in skin lesions of different clinical forms of ACL caused by L.(V.) braziliensis and L.(L.) amazonensis, with a view to a better understanding of the role of these cells in the immunopathogenesis of this important endemic disease affecting various regions of Brazil.