Dissecting interferon-induced transcriptional programs in human peripheral blood cells

Waddell, Simon J, Popper, Stephen J, Rubins, Kathleen H, Griffiths, Michael J, Brown, Patrick O, Levin, Michael and Relman, David A (2010) Dissecting interferon-induced transcriptional programs in human peripheral blood cells. PLoS ONE, 5 (3). e9753. ISSN 1932-6203

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Abstract

Interferons are key modulators of the immune system, and are central to the control of many diseases. The response of immune cells to stimuli in complex populations is the product of direct and indirect effects, and of homotypic and heterotypic cell interactions. Dissecting the global transcriptional profiles of immune cell populations may provide insights into this regulatory interplay. The host transcriptional response may also be useful in discriminating between disease states, and in understanding pathophysiology. The transcriptional programs of cell populations in health therefore provide a paradigm for deconvoluting disease-associated gene expression profiles.We used human cDNA microarrays to (1) compare the gene expression programs in human peripheral blood mononuclear cells (PBMCs) elicited by 6 major mediators of the immune response: interferons alpha, beta, omega and gamma, IL12 and TNFalpha; and (2) characterize the transcriptional responses of purified immune cell populations (CD4+ and CD8+ T cells, B cells, NK cells and monocytes) to IFNgamma stimulation. We defined a highly stereotyped response to type I interferons, while responses to IFNgamma and IL12 were largely restricted to a subset of type I interferon-inducible genes. TNFalpha stimulation resulted in a distinct pattern of gene expression. Cell type-specific transcriptional programs were identified, highlighting the pronounced response of monocytes to IFNgamma, and emergent properties associated with IFN-mediated activation of mixed cell populations. This information provides a detailed view of cellular activation by immune mediators, and contributes an interpretive framework for the definition of host immune responses in a variety of disease settings.

Item Type: Article
Additional Information: IDS Number: 573FR
Keywords: Infection Immunology Cytokine Host response Transcriptional profiling
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Brighton and Sussex Medical School > Global Health and Infection
Subjects: Q Science > QR Microbiology > QR0180 Immunology
R Medicine > R Medicine (General)
Depositing User: Simon Waddell
Date Deposited: 22 Aug 2011 13:56
Last Modified: 22 Sep 2017 11:20
URI: http://sro.sussex.ac.uk/id/eprint/7064
Google Scholar:12 Citations

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