Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.

Stephen M Christensen,Ashton T Belew,Wagner L Tafuri,David M Mosser,Fernando T Silveira,Najib M El-Sayed,Hechmi Louzir

doi:10.1371/journal.pntd.0007152

Abstract

Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses. Whereas localized disease exhibited activated (so-called M1) macrophage presence, transcripts in DCL suggested a regulatory macrophage (R-Mϕ) phenotype with higher levels of ABCB5, DCSTAMP, SPP1, SLAMF9, PPARG, MMPs, and TM4SF19. The high levels of parasite transcripts in DCL and the remarkable uniformity among patients afforded a unique opportunity to study parasite gene expression in this disease. Patterns of parasite gene expression in DCL more closely resembled in vitro parasite growth in resting macrophages, in the absence of T cells. In contrast, parasite gene expression in LCL revealed 336 parasite genes that were differently upregulated, relative to DCL and in vitro macrophage growth, and these transcripts may represent transcripts that are produced by the parasite in response to host immune pressure.

Highlights

Parasites in the genus Leishmania spp cause the spectral disease leishmaniasis, which can range from self-healing cutaneous lesions to a fatal, visceral form of disease [1,2]
American tegumentary leishmaniasis (ATL) can present in many different clinical forms, but they are classically described in four basic categories: localized cutaneous leishmaniasis (LCL); mucocutaneous leishmaniasis (MCL), disseminated leishmaniasis (DL) and anergic diffuse cutaneous leishmaniasis (DCL) [4]
L. amazonensis causes cutaneous disease, but in contrast to L. braziliensis, it can sometimes manifest as diffuse cutaneous leishmaniasis (DCL) [8,9]

Summary

Introduction

Parasites in the genus Leishmania spp cause the spectral disease leishmaniasis, which can range from self-healing cutaneous lesions to a fatal, visceral form of disease [1,2]. Manifestations of cutaneous leishmaniasis can depend on both the parasite species and host immune responses. LCL caused by Leishmania braziliensis infections typically result in a single dermal lesion, with small numbers of parasites and a strong delayed-type hypersensitivity (DTH) response [5,6]. L. amazonensis causes cutaneous disease, but in contrast to L. braziliensis, it can sometimes manifest as diffuse cutaneous leishmaniasis (DCL) [8,9]. In this rare form of the disease, parasites grow uncontrolled in lesions diffuse across the skin. While the morphology and pathology of diffuse cutaneous lesions has been studied [4], the underlying causes are not well understood

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