Impaired Th1 response is associated 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). CL patients usually present a positive LST, but as small percentage have a negative LST (LST-). The aim of this study was to determine the clinic and immunologic features and response to antimony therapy in LST- CL patients. Methods Here we compare the clinic presentation, response to therapy and immune response of CL patients with LST- versus LST+. Results The clinic presentation was similar in both groups, but LST- patients had a lower cure rate. In the lesions, LST- patients displayed less inflammation, necrosis and higher frequency of CD8+ T cells. Mononuclear cells from LST- had a poor Th1 response but levels of IL-1β, IL-6, IL-17, granzyme B and metalloproteinase-9 (MMP-9) were similar to the LST+ 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- patients, impairment in Th1 response is associated with therapeutic failure, and the increased frequency of CD8+ T cells and high production of inflammatory cytokines, granzyme B and MMP-9 contributes to immunopathology.