title: Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes.
abstract: BACKGROUND
  Mammal macrophages (MPhi) display a wide range of functions which contribute to surveying and maintaining tissue integrity. One such function is phagocytosis, a process known to be subverted by parasites like Leishmania (L). Indeed, the intracellular development of L. amazonensis amastigote relies on the biogenesis and dynamic remodelling of a phagolysosome, termed the parasitophorous vacuole, primarily within dermal MPhi.
  
  
  RESULTS
  Using BALB/c mouse bone marrow-derived MPhi loaded or not with amastigotes, we analyzed the transcriptional signatures of MPhi 24 h later, when the amastigote population was growing. Total RNA from MPhi cultures were processed and hybridized onto Affymetrix Mouse430_2 GeneChips, and some transcripts were also analyzed by Real-Time quantitative PCR (RTQPCR). A total of 1,248 probe-sets showed significant differential expression. Comparable fold-change values were obtained between the Affymetrix technology and the RTQPCR method. Ingenuity Pathway Analysis software pinpointed the up-regulation of the sterol biosynthesis pathway (p-value = 1.31e-02) involving several genes (1.95 to 4.30 fold change values), and the modulation of various genes involved in polyamine synthesis and in pro/counter-inflammatory signalling.
  
  
  CONCLUSIONS
  Our findings suggest that the amastigote growth relies on early coordinated gene expression of the MPhi lipid and polyamine pathways. Moreover, these MPhi hosting multiplying L. amazonensis amastigotes display a transcriptional profile biased towards parasite-and host tissue-protective processes.
authors.affiliation: Institut Pasteur, Unité d'Immunophysiologie et Parasitisme Intracellulaire, Département de Parasitologie et Mycologie, Paris, France. josorio@pasteur.fr
authors.forename: José
authors.initials: J
authors.lastname: Osorio y Fortéa
authors.forename: Emilie
authors.initials: E
authors.lastname: de La Llave
authors.forename: Béatrice
authors.initials: B
authors.lastname: Regnault
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Thierry
authors.initials: T
authors.lastname: Lang
authors.forename: Eric
authors.initials: E
authors.lastname: Prina
mesh_terms: D000818:Animals; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007891:Leishmania; D008264:Macrophages / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000502:physiology; D010588:Phagosomes / Q000469:parasitology; D020133:Reverse Transcriptase Polymerase Chain Reaction