Search

Introduction: Zoonotic cutaneous leishmaniasis (ZCL), due to infection by Leishmania (L). major, is characterized by polymorphic clinical manifestations which could be attributed to the host's immune response. In this study we investigated the involvement of cytotoxic cells on the outcome of the disease., Methods: Expression of granzyme B (GrB), granulysine (Grly), and interferon (IFN)-γ was evaluated within ZCL lesion specimens using the technique of real-time quantitative polymerase chain reaction (RT-qPCR). Immunohistochemical staining was performed using anti-CD3, CD4, CD8, CD56, GrB, and IFN-γ antibodies to identify the phenotype of GrB and IFN-γ-producing cells., Results: GrB and Grly mRNA was detected within 75% and 80% of ZCL lesions, respectively. Statistical analysis demonstrated a significant correlation between levels of GrB and Grly. Interestingly, expression of these molecules correlates negatively with the lesion's age. The highest levels were measured in early lesions (E-ZCL) (lesion age ≤1 month) comparing to late lesions (L-ZCL) (lesion age >1 month). Otherwise, IFN-γ mRNA was detected only within 56% and a positive correlation was found between levels of this cytokine and those of GrB. Immunohistochemical analysis showed that GrB is produced essentially by CD8 + T cells whereas IFN-γ is produced by both CD4 + and CD8 + T cells., Conclusion: Together our results demonstrate the presence of cytotoxic cells producing GrB and Grly within leishmaniasis cutaneous lesions., (© 2019 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Lesion features in cutaneous leishmaniasis (CL) depend on the infecting Leishmania species as well as on host immune reponse. In this study, we evaluated the histological and immunological differences between two forms of CL described in Tunisia: zoonotic cutaneous leishmaniasis (ZCL) caused by L. major and sporadic cutaneous leishmaniasis (SCL) caused by L. infantum. Histological analysis showed a mild to moderate infiltrate within ZCL lesions. In contrast, massive infiltration of the dermis was observed within SCL lesions. Contrary to ZCL, infiltrates within SCL lesions were organized and showed granuloma composed of macrophages and lymphocytes. In addition, immunohistochemical analysis showed a predominance of CD4 + T cells within both CL forms. Furthermore, expression of interferon-γ, interleukin (IL)-10, IL-8, IL-13 and monocyte chemotactic protein (MCP)-1 was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR). MCP-1 and IL-10 were expressed at comparable levels in ZCL and SCL lesions. Interestingly, IL-8 mRNA levels were significantly higher in ZCL lesions compared to SCL lesions, but interferon-γ was significantly higher in SCL lesions than in ZCL lesions., (© T. Boussoffara et al., published by EDP Sciences, 2019.)

Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major infection is characterized by different clinical presentations which depend in part on the host factors. In attempt to investigate the impact of the host's immune response in the outcome of the disease, we conducted a prospective study of 453 individuals living in endemic foci of L. major transmission in Central Tunisia. Several factors were assessed at the baseline including (i) the presence of typical scars of ZCL, (ii) in vivo hypersensitivity reaction to leishmanin, and (iii) the in vitro release of granzyme B (Grz B) by peripheral blood mononuclear cells (PBMC) in response to stimulation with live L. major promastigotes. After one season of parasite's transmission, repeated clinical examinations allowed us to diagnose the new emerging ZCL cases. Heterogeneity was observed in terms of number of lesions developed by each individual as well as their size and spontaneous outcome, which led us to establish the parameter "severity of the disease." The efficacy of the presence of typical ZCL scar, the leishmanin skin test (LST) positive reactivity and the high levels of Grz B (≥2 ng/ml), in the protection against the development of ZCL were 29, 15, and 22%, respectively. However, these factors were more efficient against development of intermediate or severe forms of ZCL. Levels of Grz B >2 ng/ml showed the best efficacy of protection (equals to 72.8%) against development of these forms of ZCL. The association of such parameter with the positivity of the LST exhibited a better efficacy (equals to 83.6%). In conclusion, our results support the involvement of Leishmania -specific cytotoxic cellular immune response in host protection against Leishmania -infection. This factor could be of great interest in monitoring the success of vaccination against human leishmaniasis.

To accurately quantify the different outcomes of Leishmania major infection and to evaluate the fraction of zoonotic cutaneous leishmaniasis (ZCL) cases prevented by naturally acquired leishmanin skin test (LST) reactivity, a cohort of 470 children was followed up in 2 endemic foci, Remada and Dhiba, in southern Tunisia. During May 1997, before the ZCL emergence season, LST was performed, and results were reassessed 12 months later. Active case detection during the ZCL emergence season showed a high incidence of ZCL: 57.0% in Remada and 13.7% in Dhiba. The preventive fraction of ZCL conferred by LST reactivity increased proportionally with the reaction size before the emergence season, revealing a dose-response effect of approximately 70%. In addition, asymptomatic L. major infection appeared to be a significant form of natural immunization, particularly in the context of relatively low transmission. These findings may help in the design and evaluation of vaccines.

The article presents a study which investigates the efficacy of paromomycin antibiotic for treatment of cutaneous leishmaniasis. Three types of treatments were used to test the effectivity of the antibiotic in leishmaniasis patients, including the combination of paromomycin and gentamicin, pure paromomycin, and vehicle control. Result reveal that paromomycin antibiotic is an effective treatment for ulcerative Leishmania major diseases.