title: Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
abstract: Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization, and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a data set of 299 macrophage transcriptomes. Analysis of this data set revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Jia
authors: J
authors: Xue
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Susanne V
authors: SV
authors: Schmidt
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Jil
authors: J
authors: Sander
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Astrid
authors: A
authors: Draffehn
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Wolfgang
authors: W
authors: Krebs
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Inga
authors: I
authors: Quester
authors: Institute of Innate Immunity, University Hospitals, University of Bonn, 53127 Bonn, Germany.
authors: Dominic
authors: D
authors: De Nardo
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Trupti D
authors: TD
authors: Gohel
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Martina
authors: M
authors: Emde
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Lisa
authors: L
authors: Schmidleithner
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Hariharasudan
authors: H
authors: Ganesan
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Andrea
authors: A
authors: Nino-Castro
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Michael R
authors: MR
authors: Mallmann
authors: Institute of Innate Immunity, University Hospitals, University of Bonn, 53127 Bonn, Germany.
authors: Larisa
authors: L
authors: Labzin
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Heidi
authors: H
authors: Theis
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Michael
authors: M
authors: Kraut
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Marc
authors: M
authors: Beyer
authors: Institute of Innate Immunity, University Hospitals, University of Bonn, 53127 Bonn, Germany; Division of Infectious Diseases and Immunology, UMass Medical School, Worcester, MA 01605, USA; German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany.
authors: Eicke
authors: E
authors: Latz
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh, Midlothian EH25 9RG, Scotland, UK.
authors: Tom C
authors: TC
authors: Freeman
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
authors: Thomas
authors: T
authors: Ulas
authors: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany. Electronic address: j.schultze@uni-bonn.de.
authors: Joachim L
authors: JL
authors: Schultze
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D051379:Mice; D008954:Models, Biological; D059467:Transcriptome / Q000235:genetics*