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Título : TEGUMENTARY LEISHMANIASIS: IMMUNOLOGY AND MOLECULAR BIOLOGY
Autor : Tapia, Félix J.
Díaz, NL.
Rodríguez, OI.
Sánchez, MA.
Palabras clave : Leishmaniasis
molecular biology
immunoregulation
Leishmania
Fecha de publicación : 2009
Editorial : Gazeta Médica da Bahia
Citación : ;79 (Supl.3):84-90
Resumen : The past few years have produced remarkable advances in our understanding of the skin immune response. Some better understandings of T-cell trafficking, the emerging role of Dendritic cells (DCs) and antimicrobial peptides in innate immunity, and the re-emergence of the suppressor cell as the T-regulatory cell, are changing our understanding of the immunopathology in a wide variety of cutaneous diseases and opening new opportunities to manipulate systemic immune responses through the skin. Our group has demonstrated the participation of epidermal DCs in both human and murine cutaneous leishmaniasis, and have shown that most of the tissue-damage observed in tegumentary leishmaniasis is caused by the immune response a not by the parasite. Tissue-damage that is promoted by inadequate epidermal signals directed by DCs. We have also demonstrated increased numbers of IL-10+ Langerhans cells in the lesions of patients with intermediate cutaneous leishmaniasis as compared with localized cutaneous leishmaniasis, and have shown that the adoptive transfer of splenic DCs confers protection to Leishmania-infection in a neonatal BALB/c model of the disease. The antimicrobial peptides are mechanisms of the innate immunity that contribute to the host defense. LL-37 is a peptide derived from the human cathelicidin CAP18 predominately expressed on epithelial tissue during inflammation. Besides its antibacterial function, LL-37 has a role as an inflammatory mediator that have not been studied in leishmaniasis. In this study, we evaluated the leishmanicidal activity of LL-37, its effect on the infection with L. mexicana promastigotes and murine bone marrow derived DCs, and the lymphoproliferative response against the parasite. The results suggest that LL-37 is a multifunctional regulator of the innate and adaptive immune response against L. mexicana, having a leishmanicidal activity, increasing phagocytosis on DCs and macrophages, and acting as activator or suppressor of the adaptive immune response depending on the concentration. In order to understand the immunoregulatory mechanisms that are activated after the resolution of a skin lesion in leishmaniasis, we used a single homotypic stressor just before the inoculation of Leishmania parasites in our susceptible and resistant mouse models of L. mexicana infection. The stressor consisted of immobilization by placement, for 2 or 8 hours, in restraining cages. The results suggest that stress by immobilization may modulate the genetically predetermined immune response to Leishmania parasite. In addition and perhaps more significant, it indicates that animals manage the same acute and homotypic stress in a different manner, some exacerbating their lesions and others by healing them on the basis of their genetic legacy. Studies by David Sacks’ group indicate that nTregs are essential for the development and maintenance of the persistent cutaneous infection, and reactivation of the infections caused by the Leishmania parasite
URI : http://saber.ucv.ve/jspui/handle/123456789/5431
ISSN : 0016-545X
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