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.
Key words: Leishmaniasis, molecular biology, immunoregulation, Leishmania