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

Background: Mammal macrophages (MF) 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 MF. Results: Using BALB/c mouse bone marrow-derived MF loaded or not with amastigotes, we analyzed the transcriptional signatures of M Phi 24 h later, when the amastigote population was growing. Total RNA from M Phi cultures were processed and hybridized onto Affymetrix Mouse430_2 GeneChips (R), 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 (R) 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 MF lipid and polyamine pathways. Moreover, these MF hosting multiplying L. amazonensis amastigotes display a transcriptional profile biased towards parasite-and host tissue-protective processes.