Characterization of Chronic Cutaneous Lesions from TNF-Receptor-1-Deficient Mice Infected byLeishmania major

Carolina Ferreira Oliveira,Paula Seixas Mello,Luíza Da Silva Miranda,Daniel Manzoni-De-Almeida,Caio Cotta Natale,Rosa Maria Esteves Arantes,Leda Quercia Vieira,Helton Da Costa Santiago,Liliane Martins Dos Santos,Mauro Martins Teixeira,Fernanda Oliveira Ferraz

doi:10.1155/2012/865708

Carolina Ferreira Oliveira, Paula Seixas Mello + Show 9 more

Open Access

https://doi.org/10.1155/2012/865708

Copy DOI

Abstract

Leishmania major-infected TNF receptor 1 deficient (TNFR1 KO) mice resolve parasitism but fail to resolve lesions, while wild-type mice completely heal. We investigated the cell composition, cytokine production, and apoptosis in lesions from L. major-infected TNFR1 KO and wild-type (WT) mice. Chronic lesions from L. major-infected TNFR1 KO mice presented larger number of CD8+ T and Ly6G+ cells. In addition, higher concentrations of mRNA for IFN-γ CCL2 and CCL5, as well as protein, but lower numbers of apoptotic cells, were found in lesions from TNFR1 KO mice than in WT, at late time points of infection. Our studies showed that persistent lesions in L. major-infected TNFR1 KO mice may be mediated by continuous migration of cells to the site of inflammation due to the presence of chemokines and also by lower levels of apoptosis. We suggest that this model has some striking similarities to the mucocutaneous clinical form of leishmaniasis.

Highlights

Parasites of the genus Leishmania cause a spectrum of cutaneous manifestations ranging from limited cutaneous lesions that heal spontaneously to the more severe mucocutaneous form
It is established that BALB/c mice are susceptible to infection by Leishmania major
Resistance to infection by L. major is mediated by IFN-γ, TNF-α, and activation of macrophages to produce nitric oxide [4,5,6]

Summary

Introduction

Parasites of the genus Leishmania cause a spectrum of cutaneous manifestations ranging from limited cutaneous lesions that heal spontaneously to the more severe mucocutaneous form. These different clinical manifestations depend on the species of Leishmania and the host immune response [1, 2]. It is established that BALB/c mice are susceptible to infection by Leishmania major. This mouse strain develops progressive lesions, uncontrolled growth of parasites, visceralization, and death. The C57BL/6 strain is resistant to infection by L. major, controls parasite replication, and heals lesions [3]. Resistance to infection by L. major is mediated by IFN-γ, TNF-α, and activation of macrophages to produce nitric oxide [4,5,6]

Objectives

Methods

Results

Conclusion