Transcriptional and Linkage Analyses Identify Loci that Mediate the Differential Macrophage Response to Inflammatory Stimuli and Infection

• DOI: 10.1371/journal.pgen.1005619
• Publication Date: 2015-10-28T20:36:01Z
• Authors: Musa A. Hassan; Kirk D. Jensen; Vincent Butty; Kenneth Hu; Erwan Boedec; Pjotr Prins; Jeroen P. J. Saeij
• Keywords: Macrophage polarization; Intracellular parasite

Macrophages display flexible activation states that range between pro-inflammatory (classical activation) and anti-inflammatory (alternative activation). These macrophage polarization contribute to a variety of organismal phenotypes such as tissue remodeling susceptibility infectious inflammatory diseases. Several macrophage- or immune-related genes have been shown modulate disease pathogenesis. However, the potential role differences in play modulating is just emerging. We integrated transcriptional profiling linkage analyses determine genetic basis for differential murine response stimuli infection with obligate intracellular parasite Toxoplasma gondii. show specific programs, defined by distinct genomic loci, phenotypes. In addition, we difference AJ C57BL/6J macrophages controlling growth after stimulation interferon gamma tumor necrosis factor alpha mapped chromosome 3, proximal Guanylate binding protein (Gbp) locus known Toxoplasma. Using an shRNA-knockdown strategy, transcript levels RNA helicase, Ddx1, regulates strain amount nitric oxide produced factor. Our results provide template discovering candidate macrophage-mediated complex traits.