Changes in Macrophage Gene Expression Associated with Leishmania (Viannia) braziliensis Infection.

Clemencia Ovalle-Bracho,Carlos Clavijo-Ramírez,Daniel Restrepo-Montoya,Carlos Franco-Muñoz,Diana Londoño-Barbosa,Yara M Traub-Csekö

doi:10.1371/journal.pone.0128934

Clemencia Ovalle-Bracho, Carlos Clavijo-Ramírez + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0128934

Copy DOI

Abstract

Different Leishmania species cause distinct clinical manifestations of the infectious disease leishmaniasis. It is fundamentally important to understand the mechanisms governing the interaction between Leishmania and its host cell. Little is known about this interaction between Leishmania (Viannia) braziliensis and human macrophages. In this study, we aimed to identify differential gene expression between non-infected and L. (V) braziliensis-infected U937-derived macrophages. We deployed a whole human transcriptome microarray analysis using 72 hours post-infection samples and compared those samples with their non-infected counterparts. We found that 218 genes were differentially expressed between infected and non-infected macrophages. A total of 71.6% of these genes were down-regulated in the infected macrophages. Functional enrichment analyses identified the steroid and sterol/cholesterol biosynthetic processes between regulatory networks down-regulated in infected macrophages. RT-qPCR further confirmed this down-regulation in genes belonging to these pathways. These findings contrast with those from studies involving other Leishmania species at earlier infection stages, where gene up-regulation for this metabolic pathway has been reported. Sterol biosynthesis could be an important biological process associated with the expression profile of macrophages infected by L. (V.) braziliensis. Differential transcriptional results suggest a negative regulation of the genetic regulatory network involved in cholesterol biosynthesis.

Highlights

American tegumentary leishmaniasis is a public health problem in Central and South America, affecting 18 countries with approximately 1.5 million new cases each year
The objective of this work was to determine the global gene expression profile of macrophages derived from the U937 cell line associated with L. (V.) braziliensis infection and to identify, based on functional enrichment analysis, the biological processes linked to the genes differentially expressed between non-infected macrophages and those infected for 72 hours
Identification of genes differentially expressed by infected versus noninfected macrophages Leishmania is capable of modulating the immune response and the signaling pathways of macrophages to promote its survival in the host cell

Summary

Introduction

American tegumentary leishmaniasis is a public health problem in Central and South America, affecting 18 countries with approximately 1.5 million new cases each year. Brazil and Peru present 75% of the cases of cutaneous leishmaniasis in Latin America [1]. Species within the Viannia subgenus are prevalent in America and are linked to cutaneous and mucocutaneous leishmaniasis, with L. (V.) braziliensis being the major etiological agent of the latter. MRNA Levels in Infected Macrophages by L. (V.) braziliensis design, data collection and analysis, decision to publish, or preparation of the manuscript Species within the Viannia subgenus are prevalent in America and are linked to cutaneous and mucocutaneous leishmaniasis, with L. (V.) braziliensis being the major etiological agent of the latter.

Objectives

Methods

Results

Conclusion