title: Changes in Macrophage Gene Expression Associated with Leishmania (Viannia) braziliensis Infection.
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.
authors.affiliation: Centro Dermatológico Federico Lleras Acosta, Bogotá, Colombia; Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Clemencia
authors.initials: C
authors.lastname: Ovalle-Bracho
authors.affiliation: Centro Dermatológico Federico Lleras Acosta, Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Franco-Muñoz
authors.affiliation: Centro Dermatológico Federico Lleras Acosta, Bogotá, Colombia.
authors.forename: Diana
authors.initials: D
authors.lastname: Londoño-Barbosa
authors.affiliation: Centro Dermatológico Federico Lleras Acosta, Bogotá, Colombia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Restrepo-Montoya
authors.affiliation: Departamento de Biología, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Clavijo-Ramírez
mesh_terms: D002784:Cholesterol / Q000096:biosynthesis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007892:Leishmania braziliensis / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000469:parasitology*; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020298:U937 Cells
chemical_list: D002784:Cholesterol