title: Human macrophage response to L. (Viannia) panamensis: microarray evidence for an early inflammatory response.
abstract: BACKGROUND
  Previous findings indicate that susceptibility to Leishmania (Viannia) panamensis infection of monocyte-derived macrophages from patients and asymptomatically infected individuals were associated with the adaptive immune response and clinical outcome.
  
  
  RESULTS
  To understand the basis for this difference we examined differential gene expression of human monocyte-derived macrophages following exposure to L. (V.) panamensis. Gene activation profiles were determined using macrophages from healthy volunteers cultured with or without stationary phase promastigotes of L. (V.) panamensis. Significant changes in expression (>1.5-fold change; p<0.05; up- or down-regulated) were identified at 0.5, 4 and 24 hours. mRNA abundance profiles varied over time, with the highest level of activation occurring at earlier time points (0.5 and 4 hrs). In contrast to observations for other Leishmania species, most significantly changed mRNAs were up- rather than down-regulated, especially at early time points. Up-regulated transcripts over the first 24 hours belonged to pathways involving eicosanoid metabolism, oxidative stress, activation of PKC through G protein coupled receptors, or mechanism of gene regulation by peroxisome proliferators via PPARα. Additionally, a marked activation of Toll-receptor mediated pathways was observed. Comparison with published microarray data from macrophages infected with L. (Leishmania) chagasi indicate differences in the regulation of genes involved in signaling, motility and the immune response.
  
  
  CONCLUSIONS
  Results show that the early (0.5 to 24 hours) human monocyte-derived macrophage response to L. (Viannia) panamensis is not quiescent, in contrast to published reports examining later response times (48-96 hours). Early macrophage responses are important for the developing cellular response at the site of infection. The kinetics and the mRNA abundance profiles induced by L. (Viannia) panamensis illustrate the dynamics of these interactions and the distinct biologic responses to different Leishmania species from the outset of infection within their primary host cell.
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ramírez
authors.forename: Yira
authors.initials: Y
authors.lastname: Díaz-Toro
authors.forename: Jair
authors.initials: J
authors.lastname: Tellez
authors.forename: Tiago M
authors.initials: TM
authors.lastname: Castilho
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rojas
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Ettinger
authors.forename: Irina
authors.initials: I
authors.lastname: Tikhonova
authors.forename: Neal D
authors.initials: ND
authors.lastname: Alexander
authors.forename: Liliana
authors.initials: L
authors.lastname: Valderrama
authors.forename: Janet
authors.initials: J
authors.lastname: Hager
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wilson
authors.forename: Aiping
authors.initials: A
authors.lastname: Lin
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Saravia
authors.forename: Diane
authors.initials: D
authors.lastname: McMahon-Pratt
mesh_terms: D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D018334:Leishmania guyanensis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors
chemical_list: D012333:RNA, Messenger