Impaired Th1 Response Is Associated With Therapeutic Failure in Patients With Cutaneous Leishmaniasis Caused by Leishmania braziliensis.

BACKGROUND: Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). In CL patients LST is usually positive but a small percentage have negative LST. The aim of this study was to determine the clinical and immunologic features and response to antimony therapy in LST-negative CL patients. METHODS: We compare the clinical presentation, response to therapy, and immune response of CL patients with negative vs positive LST. RESULTS: The clinical presentation was similar in both groups but LST-negative patients had a lower cure rate. In the lesions, LST-negative patients displayed less inflammation and necrosis, and higher frequency of CD8+ T cells. Mononuclear cells from LST-negative patients had a poor T helper 1 cell (Th1) response but levels of interleukin-1ß (IL-1ß), IL-6, IL-17, granzyme B, and metalloproteinase-9 (MMP-9) were similar to the LST-positive group upon stimulation with LA. Leishmania internalization and killing by macrophages were similar in both groups. Cure of disease was associated with restoration of Th1 response. CONCLUSIONS: In LST-negative patients, impaired Th1 response is associated with therapeutic failure. Increased frequency of CD8+ T cells and high production of inflammatory cytokines, granzyme B, and MMP-9 contributes to immunopathology.

Characterization of the Histopathologic Features in Patients in the Early and Late Phases of Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL), characterized by an ulcerated lesion, is the most common clinical form of human leishmaniasis. Before the ulcer develops, patients infected with Leishmania (Viannia) braziliensis present a small papule at the site of the sandfly bite, referred to as early cutaneous leishmaniasis (E-CL). Two to four weeks later the typical ulcer develops, which is considered here as late CL (L-CL). Although there is a great deal known about T-cell responses in patients with L-CL, there is little information about the in situ inflammatory response in E-CL. Histological sections of skin biopsies from 15 E-CL and 28 L-CL patients were stained by hematoxilin and eosin to measure the area infiltrated by cells, as well as tissue necrosis. Leishmania braziliensis amastigotes, CD4+, CD8+, CD20+, and CD68+ cells were identified and quantified by immunohistochemistry. The number of amastigotes in E-CL was higher than in L-CL, and the inflammation area was larger in classical ulcers than in E-CL. There was no relationship between the number of parasites and magnitude of the inflammation area, or with the lesion size. However, there was a direct correlation between the number of macrophages and the lesion size in E-CL, and between the number of macrophages and necrotic area throughout the course of the disease. These positive correlations suggest that macrophages are directly involved in the pathology of L. braziliensis-induced lesions.