CD14 is a key organizer of microglial responses to CNS infection and injury
18.12.2015 Janova H, Böttcher C, Holtman IR, Regen T, van Rossum D, Götz A, Ernst AS, Fritsche C, Gertig U, Saiepour N, Gronke K, Wrzos C, Ribes S, Rolfes S, Weinstein J, Ehrenreich H, Pukrop T, Kopatz J, Stadelmann C, Salinas-Riester G, Weber MS, Prinz M, Brück W, Eggen BJ, Boddeke HW, Priller J, Hanisch UK. Glia. 2016;64(4):635-49. Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon ?-mediated feedback. While CD14 orchestrates functions of TLR4 and related immune receptors, it is itself regulated by TLR and non-TLR systems to thereby fine-tune microglial damage-sensing capacity upon infectious and non-infectious CNS challenges. 