Skip to main content
. 2017 Nov 10;8:1520. doi: 10.3389/fimmu.2017.01520

Figure 1.

Figure 1

Key stimuli and molecular pathways in inflammatory vs. resolution phenotype in mononuclear phagocytes. Inflammatory and resolution macrophage phenotype results as external stimuli are integrated via signaling pathways to drive phenotype-supporting transcriptional programs and cellular metabolism. Red and blue color indicates pathways, stimuli, transcription factors and metabolic processes associated with inflammatory or resolution phenotype, respectively. Inflammatory phenotype is induced or promoted by pathogens, injured cells and in vitro stimuli. In contrast, resolution spectrum phenotypes are induced or promoted by parasites, fungi, apoptotic cells, immune complexes and other cytokine/growth factor stimuli. Pathogen or injury signals sensed via pathogen-recognition receptors (PRR) such as Toll-like receptors (TLR) result in Janus activated kinase (Jak)2 and nuclear factor kappa B (NF-κB) activation. Signals received via Notch receptors, cytokine receptor (CtkR), chemokine receptor (CCR), and Fc receptor (FcR) stimulation are also integrated, defining gene expression and downstream metabolic reprogramming. Interferon regulatory factors (IRFs) 5 and 8 promote inflammatory gene expression while IRF 4 promotes resolution phenotype genes. Gene expression promotes changes in nutrient uptake and metabolic pathways that support inflammatory or resolution macrophage phenotype. LPS, lipopolysaccharide; IFN-γ: interferon-γ; GM-CSF, granulocyte monocyte colony stimulation factor; IC, immune complexes; TGF-β, transforming growth factor-β; IL, interleukin; IL-1R, interleukin 1 receptor; M-CSF, monocyte colony stimulation factor; PI3K, phosphoinositide 3 kinase; AKT, serine threonine kinase; mTOR, mammalian target of rapamycin; PTEN, phosphatase and tensin homolog; TSC, tuberous sclerosis complex; c-MYC, PPAR, peroxisome proliferator activated receptor; ADAM, A disintegrin and metalloproteinase; RBP-J, recombination signal binding protein for immunoglobulin kappa J region; MAML, mastermind-like; Rictor, rapamycin-insensitive companion of mTOR; TCA, tricarboxylic acid/Krebs cycle.