Common genetic variants modulate pathogen-sensing responses in human dendritic cells.
نویسندگان
چکیده
Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-β (IFN-β). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.
منابع مشابه
The Effects of Candida Albicans Cell Wall Protein Fraction on Dendritic Cell Maturation
Back ground: Candida albicans is a member of the normal human microflora. C. albicans cell wall is composed of several protein and carbohydrate components which have been shown to play a crucial role in C. albicans interaction with the host immune system. Major components of C. albican cell wall are carbohydrates such as mannans, β glucans and chitins, and proteins that partially modulate the h...
متن کاملPathogen-sensing and regulatory T cells: integrated regulators of immune responses.
We present the concept that pathogen-sensing and regulatory T cells (Treg) mutually regulate immune responses to conventional and tumor antigens through countervailing effects on dendritic cells (DC). Normally, conventional CD4 T cells recognizing their cognate antigen presented by a DC will respond only if the DC also receives a signal through its pathogen-sensing/danger/adjuvant recognition s...
متن کاملA statistical framework for revealing signaling pathways perturbed by DNA variants
Much of the inter-individual variation in gene expression is triggered via perturbations of signaling networks by DNA variants. We present a novel probabilistic approach for identifying the particular pathways by which DNA variants perturb the signaling network. Our procedure, called PINE, relies on a systematic integration of established biological knowledge of signaling networks with data on ...
متن کاملGeneration of Mature Monocyte-Derived Dendritic Cells in the Presence of Heparin and Monocyte Conditioned Medium: Phenotypic and Functional Comparison
Background: Dendritic cells (DC) induce tumor or pathogen-specific T cell responses in humans. Several laboratories have developed culture systems, including maturation factors for human DC from peripheral blood monocytes. We comprehensively compared standard maturation stimulus, an autologous monocyte-conditioned medium (MCM), with heparin for their ability to promote uniformly mature DC that ...
متن کاملHuman Leukocyte Antigen-G Expression on Dendritic Cells Induced by Transforming Growth Factor-β1 and CD4+ T Cells Proliferation
Background: During antigen capture and processing, mature dendritic cells (DC) express large amounts of peptide-MHC complexes and accessory molecules on their surface. DC are antigen-presenting cells that have an important role in tolerance and autoimmunity. The transforming growth factor-beta1 (TGF-β1) cytokine has a regulatory role on the immune and non-immune cells. The aim of this study is ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Science
دوره 343 6175 شماره
صفحات -
تاریخ انتشار 2014