Research article

Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes

José Osorio y Fortéa¹ , Emilie de La Llave¹ , Béatrice Regnault² , Jean-Yves Coppée² , Geneviève Milon¹ , Thierry Lang^1* and Eric Prina^1*

¹  Institut Pasteur, Unité d'Immunophysiologie et Parasitisme Intracellulaire, Département de Parasitologie et Mycologie, 25 rue du Docteur Roux, 75724 Paris, France

²  Institut Pasteur, Génopole Plate-Forme 2, Puces à ADN, 28 rue du Docteur Roux, 75724 Paris, France

author email corresponding author email* Contributed equally

BMC Genomics 2009, 10:119doi:10.1186/1471-2164-10-119

Published:	20 March 2009

Abstract

Background

Mammal macrophages (MΦ) 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 MΦ.

Results

Using BALB/c mouse bone marrow-derived MΦ loaded or not with amastigotes, we analyzed the transcriptional signatures of MΦ 24 h later, when the amastigote population was growing. Total RNA from MΦ 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.

Conclusion

Our findings suggest that the amastigote growth relies on early coordinated gene expression of the MΦ lipid and polyamine pathways. Moreover, these MΦ hosting multiplying L. amazonensis amastigotes display a transcriptional profile biased towards parasite-and host tissue-protective processes.