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Published online before print October 2, 2003
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: an overview of signals, mechanisms and functions
,
,1
* Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, Australia;
CRC for Chronic Inflammatory Diseases, Parkville, Victoria, Australia; and
Molecular Genetics Group, Institute of Reproduction and Development, Monash Medical Centre, Monash University, Clayton, Victoria, Australia
1 Correspondence: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia. E-mail: D.Hume{at}imb.uq.edu.au
Interferon-
(IFN-) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN- ligand, receptor, signal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN- signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN- are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-
, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.
Key Words: macrophage • cytokine • lipopolysaccharide • Toll-like receptor • inflammation
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