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Global gene expression profiling using total RNA [BMM, MPI and SPG]

ABSTRACT: Differentiation of myeloid progenitor cells leads to distinct populations of mononuclear phagocytes.Various macrophages exhibit distinct biological properties. Here wanted to delineate and characterize gene expression patterns in bone marrow derived macrophages Here wanted to delineate and characterize gene expression patterns in two newly established, self-renewing, in vitro grown non-transformed lines (MPI cells) and in the SP37A3 immature myeloid dendritic cell line. We used microarrays to detail the global programme of gene expression in MPI cells and to compare them to other types of mononuclear phagocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE47473 | GEO | 2013/06/08

SECONDARY ACCESSION(S): PRJNA207510

REPOSITORIES: GEO

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Project description:Casandra W. Philipson, Josep Bassaganya-Riera, Monica Viladomiu, Barbara Kronsteiner, Vida Abedi, Stefan Hoops, Pawel Michalak, Lin Kang, Stephen E. Girardin & Raquel Hontecillas. Modeling the Regulatory Mechanisms by Which NLRX1 Modulates Innate Immune Responses to Helicobacter pylori Infection. PLOS ONE 10, 9 (2015). Helicobacter pylori colonizes half of the world's population as the dominant member of the gastric microbiota resulting in a lifelong chronic infection. Host responses toward the bacterium can result in asymptomatic, pathogenic or even favorable health outcomes; however, mechanisms underlying the dual role of H. pylori as a commensal versus pathogenic organism are not well characterized. Recent evidence suggests mononuclear phagocytes are largely involved in shaping dominant immunity during infection mediating the balance between host tolerance and succumbing to overt disease. We combined computational modeling, bioinformatics and experimental validation in order to investigate interactions between macrophages and intracellular H. pylori. Global transcriptomic analysis on bone marrow-derived macrophages (BMDM) in a gentamycin protection assay at six time points unveiled the presence of three sequential host response waves: an early transient regulatory gene module followed by sustained and late effector responses. Kinetic behaviors of pattern recognition receptors (PRRs) are linked to differential expression of spatiotemporal response waves and function to induce effector immunity through extracellular and intracellular detection of H. pylori. We report that bacterial interaction with the host intracellular environment caused significant suppression of regulatory NLRC3 and NLRX1 in a pattern inverse to early regulatory responses. To further delineate complex immune responses and pathway crosstalk between effector and regulatory PRRs, we built a computational model calibrated using time-series RNAseq data. Our validated computational hypotheses are that: 1) NLRX1 expression regulates bacterial burden in macrophages; and 2) early host response cytokines down-regulate NLRX1 expression through a negative feedback circuit. This paper applies modeling approaches to characterize the regulatory role of NLRX1 in mechanisms of host tolerance employed by macrophages to respond to and/or to co-exist with intracellular H. pylori.

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Global gene expression profiling using total RNA [BMM, MPI and SPG]

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