Abstract
BackgroundMammal 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.ResultsUsing 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.ConclusionOur 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.
Highlights
Mammal macrophages (MΦ) display a wide range of functions which contribute to surveying and maintaining tissue integrity
In this study we sought to analyze the transcriptional signatures of a homogeneous population of MΦ derived in vitro from BALB/c mouse bone marrow CSF-1 dependent progenitors and hosting amastigotes that are actively multiplying
The Affymetrix GeneChip technology was used to compare the gene expression profiles of L. amazonensis amastigotes-hosting bone marrow-derived MΦ and parasite-free ones. This in vitro transcriptomics approach was combined with the Ingenuity biological network analysis to highlight the mouse MΦ biological processes the multiplying L. amazonensis amastigotes rely on within their giant communal parasitophorous vacuole (PV)
Summary
Mammal macrophages (MΦ) display a wide range of functions which contribute to surveying and maintaining tissue integrity. BMC Genomics 2009, 10:119 http://www.biomedcentral.com/1471-2164/10/119 before the development of the more or less transient skin damages that characterize cutaneous leishmaniasis there is an asymptomatic phase lasting for several days or weeks during which the intracellular amastigote progeny expands This expansion takes place within a compartment named parasitophorous vacuole (PV) that displays properties similar to late endosomes/lysosomes and the size of which grows significantly for Leishmania belonging to the mexicana complex [1,2]. The Affymetrix GeneChip technology was used to compare the gene expression profiles of L. amazonensis amastigotes-hosting bone marrow-derived MΦ and parasite-free ones This in vitro transcriptomics approach was combined with the Ingenuity biological network analysis to highlight the mouse MΦ biological processes the multiplying L. amazonensis amastigotes rely on within their giant communal PV. Our findings suggest that MΦ hosting multiplying amastigotes contribute to carve a parasite-as well as a host tissue-protective environment
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