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

Rabhi, I., Rabhi, S., Ben-Othman, R., Aniba, M. R., Sysco Consortium, Herwig, R., et al. (2013). Comparative analysis of resistant and susceptible macrophage gene expression response to Leishmania major parasite. BMC Genomics, 14: 14:723. doi:10.1186/1471-2164-14-723.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-0202-A Version Permalink: http://hdl.handle.net/21.11116/0000-0001-0203-9
Genre: Journal Article

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© 2013 Rabhi et al

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 Creators:
Rabhi, Imen , Author
Rabhi, Sameh , Author
Ben-Othman, Rym , Author
Aniba, Mohamed Radhouane , Author
Sysco Consortium, Author
Herwig, Ralf1, Author              
Trentin, Bernadette , Author
Piquemal, David , Author
Regnault, Béatrice , Author
Guizani-Tabbane, Lamia , Author
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              

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Free keywords: Microarray, Macrophages, Leishmania, Gene expression
 Abstract: Background Leishmania 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. Results Here 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. Conclusions Taken 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.

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Language(s): eng - English
 Dates: 2013-10-22
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1186/1471-2164-14-723
PMC: PMC4007596
PMID: 24148319
 Degree: -

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Title: BMC Genomics
Source Genre: Journal
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Publ. Info: BioMed Central
Pages: - Volume / Issue: 14 Sequence Number: 14:723 Start / End Page: - Identifier: ISSN: 1471-2164
CoNE: /journals/resource/111000136905010