Fig. 1: The TNF response to LPS is heterogeneous and requires intercellular communication.
From: Macrophages employ quorum licensing to regulate collective activation
a The diagram summarizes the perturbations and stimuli applied to investigate TNF expression and intercellular communication (hps, hours post-stimulation with LPS). LPS activates TLR4 signaling, which induces TNF expression. IL-10 pretreatment activates IL-10R signaling, which inhibits LPS-induced TNF expression. Secreted TNF activates TNFR signaling, which induces TNF further through intercellular feedback. BFA prevents secretion, causing TNF to accumulate intracellularly. Varying the cell density modulates the concentrations of secreted factors such as TNF. sTNFR binds extracellular TNF and prevents TNFR signaling. b IL-10 pretreatment diminishes LPS-induced TNF expression. c TNF expression is heterogeneous with high-expressing and low-expressing subpopulations. After pretreatment with IL-10 (10 ng ml–1) and/or treatment with LPS (100 ng ml–1), cells were treated with BFA for 1 or 2 h. Arrows in c–e indicate low and high modes of the TNF distributions. d The full TNF response to LPS requires intercellular communication. e Intercellular feedback through secreted TNF is necessary for the full response. Source data are provided as a Source Data file.
