LINC01857 regulates antigen-presenting cell viability and antimicrobial defense in humans

Here, we identify LINC01857, a primate-specific lincRNA, as a critical modulator of macrophage survival and antimicrobial defense. LINC01857 is induced during monocyte-to-macrophage differentiation but rapidly downregulated upon bacterial challenge via NFκB. Under homeostatic conditions, it dampens adhesion, phagocytosis and invasion factors, including SIGLEC1 and MMP7, and suppresses apoptosis.

Loss of LINC01857 during infection creates a 'dead-end' niche that limits Salmonella Typhimurium intracellular replication, whereas enforced expression promotes pathogen propagation. Mechanistically, LINC01857 interacts with the adaptor protein 14-3-3β to support macrophage survival. Notably, downregulation of LINC01857 is mirrored in circulating immune cells from patients with severe COVID-19 and sepsis.