Abstract

In Honduras, Leishmania (L.) infantum chagasi causes both visceral leishmaniasis (LV) and nonulcerated or atypical cutaneous leishmaniasis (NUCL). NUCL is characterized by mononuclear inflammatory infiltration of the dermis, composed mainly of lymphocytes followed by macrophages with discrete parasitism. Considering that little is known about the pathogenesis of NUCL, the aim of this study was to evaluate the regulatory response in situ in skin lesions of patients affected by NUCL. Biopsies (n = 20) from human cutaneous nonulcerative lesions were collected and processed by usual histological techniques. The in situ regulatory immune response was evaluated by immunohistochemistry using antihuman CD4, FoxP3, IL-10, and TGF-β antibodies. CD4+, FoxP3+, TGF-β+, and IL-10+ cells were observed in the dermis with inflammatory infiltration in all studied cases and at higher densities compared to the normal skin controls. A positive and strong correlation was observed between CD4+ and FoxP3+ cells, and a positive and moderate correlation was observed between FoxP3+ and TGF-β+ but not with IL-10+ cells. The data suggest that T regulatory FoxP3+ cells and the regulatory cytokines, especially TGF-β, play an important role in the immunopathogenesis of NUCL, modulating a cellular immune response in the skin, avoiding tissue damage, and leading to low tissue parasitic persistence.

Highlights

  • Nonulcerated cutaneous leishmaniasis (NUCL) is a rare form of leishmaniasis described in areas of visceral leishmaniasis (VL) transmission in Central America, including Honduras, Costa Rica, El Salvador, and Nicaragua

  • Nonulcerated or atypical cutaneous leishmaniasis is a rare clinical form of infection caused by Leishmania (L.) infantum chagasi, and interestingly, it has been described only in Central America

  • In Honduras, infection caused by Leishmania (L.) infantum chagasi is restricted to the southern region of the country, where cases of VL and NUCL occur in the same geographic area [1]

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Summary

Introduction

Nonulcerated cutaneous leishmaniasis (NUCL) is a rare form of leishmaniasis described in areas of visceral leishmaniasis (VL) transmission in Central America, including Honduras, Costa Rica, El Salvador, and Nicaragua. The lesions are characterized by small nonulcerative erythematous papules or erythematous plaques of chronic evolution that are between 1 to 10 mm in diameter and are located in exposed areas of the body, especially the face and extremities, often surrounded by a hypopigmented halo. The main tissue features have been characterized by a granulomatous reaction with a small number of amastigote forms of the parasite [2]. It is important to mention that the identification of Leishmania isolates from NUCL lesions from Honduras showed that parasites belong to the Leishmania donovani complex by specific monoclonal antibodies, and they were

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