Cellular infiltrate in cutaneous leishmaniasis lesions and therapeutic outcome

Abstract

Background The treatment of cutaneous leishmaniasis is a challenge. A better understanding of the in situ mechanisms involved in the evolution and cure of the disease is essential for the development of new therapies. Objective Correlate histopathological and immunological characteristics of cutaneous leishmaniasis lesions with clinical outcome after different treatment regimens. Methods The authors analyzed cellular infiltration and immunohistochemistry staining for CD4, CD8 and IL-17 in biopsy samples from 33 patients with cutaneous leishmaniasis before treatment. All patients were recruited in a randomized clinical trial at Corte de Pedra (Bahia-Brazil) and assigned to receive Glucantime®, Glucantime® + Oral Tamoxifen or Glucantime® + Topical Tamoxifen. Patients were followed for 2 to 6 months to define disease outcome. Results A similar expression of CD4, CD8 and IL-17 was observed in lesion samples regardless of clinical outcome. In general, a higher amount of CD8 cells were observed compared with CD4 cells. An important observation was that all patients whose cellular infiltrate did not contain plasma cells were cured after treatment. Study limitations Isolated quantification of TCD8 and IL-17 using immunohistochemistry is insufficient to analyze the role of these molecules in the immunopathogenesis of cutaneous leishmaniasis. In addition, the expansion of the immunohistochemistry panel would allow a more complete analysis of the immune response in situ. Conclusions The absence of plasma cells in cutaneous leishmaniasis lesions was related to a favorable therapeutic outcome.

Tamoxifen Twists Again: On and Off-Targets in Macrophages and Infections

“…Although still preliminary, these cellular and molecular responses are triggered by concentrations of tamoxifen that are ensured in the clinical practice by therapeutic regimens that use higher, yet safe and well tolerated, dosages than those used in breast cancer ( Skapek et al, 2013 ; Odia et al, 2015 ; Ngan et al, 2019 ). These data strongly support the hypothesis that the immune-mediated effects of tamoxifen contribute to the efficacy of this drug against a wide spectrum of pathogen infections and sustain tamoxifen repurposing in infectious diseases, alone or in combination with standard treatments ( Machado et al, 2018 ; Ngan et al, 2019 ; Ribeiro et al, 2021 ).…”