Comparative analysis of resistant and susceptible macrophage gene expression response to Leishmania majorparasite

BMC Genomics

Research Article

Béatrice Regnault¹  Imen Rabhi²  Sameh Rabhi²  Lamia Guizani-Tabbane²  Rym Ben-Othman²  Mohamed Radhouane Aniba³  David Piquemal⁴  Bernadette Trentin⁴ 

[1] DNA Chip Platform, Genopole, Institut Pasteur de Paris, 25-28 rue du Dr Roux, 75015, Paris, France;Institut Pasteur de Tunis. Parasitologies medicales biotechnologies et Biomolecules, B. P. 74, 13, Place Pasteur, 1002, Tunis-Belvedere, Tunisia;Institute for Advanced Computer Studies Center for Bioinformatics and Computational Biology (CBCB), University of Maryland, 20742, College Park, MD, USA;Skuldtech. Cap Delta - ZAC Euromedecine II, 1682, rue de la Valsière, 34790, Grabels, France;

关键词: Microarray;    Macrophages;    Leishmania;    Gene expression;   

DOI  :  10.1186/1471-2164-14-723

 received in 2013-02-13, accepted in 2013-10-14,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundLeishmania are obligated intracellular pathogens that replicate almost exclusively in macrophages. The outcome of infection depends largely on parasite pathogenicity and virulence but also on the activation status and genetic background of macrophages. Animal models are essential for a better understanding of pathogenesis of different microbes including Leishmania.ResultsHere we compared the transcriptional signatures of resistant (C57BL/6) and susceptible (BALB/c) mouse bone marrow-derived macrophages in response to Leishmania major (L. major) promastigotes infection.Microarray results were first analyzed for significant pathways using the Kyoto Encylopedia of Genes and Genomes (KEGG) database. The analysis revealed that a large set of the shared genes is involved in the immune response and that difference in the expression level of some chemokines and chemokine receptors could partially explain differences in resistance. We next focused on up-regulated genes unique to either BALB/c or C57BL/6 derived macrophages and identified, using KEGG database, signal transduction pathways among the most relevant pathways unique to both susceptible and resistant derived macrophages. Indeed, genes unique to C57BL/6 BMdMs were associated with target of rapamycin (mTOR) signaling pathway while a range of genes unique to BALB/c BMdMs, belong to p53 signaling pathway. We next investigated whether, in a given mice strain derived macrophages, the different up-regulated unique genes could be coordinately regulated. Using GeneMapp Cytoscape, we showed that the induced genes unique to BALB/c or C57BL/6 BMdMs are interconnected. Finally, we examined whether the induced pathways unique to BALB/c derived macrophages interfere with the ones unique to C57BL/6 derived macrophages. Protein-protein interaction analysis using String database highlights the existence of a cross-talk between p53 and mTOR signaling pathways respectively specific to susceptible and resistant BMdMs.ConclusionsTaken together our results suggest that strains specific pathogenesis may be due to a difference in the magnitude of the same pathways and/or to differentially expressed pathways in the two mouse strains derived macrophages. We identify signal transduction pathways among the most relevant pathways modulated by L. major infection, unique to BALB/c and C57BL/6 BMdM and postulate that the interplay between these potentially interconnected pathways could direct the macrophage response toward a given phenotype.

【 授权许可】

Unknown   
© Rabhi et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.