Immunity Against Leishmania major Infection: Parasite-Specific Granzyme B Induction as a Correlate of Protection

Thouraya Boussoffara,Melika Ben Ahmed,Mourad Mokni,Sadok Chelif,Koussay Dellagi,Afif Ben Salah,Hechmi Louzir

doi:10.3389/fcimb.2018.00397

Abstract

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.

Highlights

Cutaneous leishmaniasis are parasitic infections caused by different species of Leishmania parasite and grouping distinct clinical manifestations
Levels of granzyme B (Grz B) Produced by peripheral blood mononuclear cells (PBMC) Stimulated With L. major Promastigotes
This was done by measurement of Grz B level in supernatants of PBMCs stimulated for 5 days with promastigotes of L. major at a ratio of 3 parasites per cell

Summary

Introduction

Cutaneous leishmaniasis are parasitic infections caused by different species of Leishmania parasite and grouping distinct clinical manifestations. In Tunisia, ZCL is due to infection by the parasite L. major zymodeme MON-25 and transmitted by Phlebotomus papatasi (Ben Ismail and Ben Rachid, 1989). ZCL takes place as seasonal epidemics with an annual prevalence ranging from 2 to 10. The clinical features of ZCL are rather polymorphic, ranging from benign self-limited to wide cutaneous lesions that may cause severe disfigurement. Human’s infection by Leishmania might be asymptomatic, in endemic areas (Ben Salah et al, 2005). The outcome of the Leishmania-infection depends partly on the type and intensity of the host immune response. The Leishmania-specific immunity associated with healing often provides a resistance to subsequent infection (Guirges, 1971; Davies et al, 1995)

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