The excessive proinflammatory responses in sepsis and associated acute respiratory distress syndrome (ARDS) are largely mediated by Toll-like receptors (TLRs). Spence et al. report a novel approach to harness the TLR inhibitory effects of sialic acid-binding immunoglobulin-like lectin E (Siglec-E) — a transmembrane receptor found on macrophages and neutrophils. Nanoparticles decorated with the Siglec E-specific ligand, α2,8-linked N-acetylneuraminic acid, reduced inflammation and prolonged survival in mouse sepsis and ARDS models and attenuated pulmonary oedema in a human ex vivo lung perfusion model of lung injury.