Macrophages play a major role in the control and elimination of invading Mycobacterium tuberculosis (Mtb). Emerging studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in resident macrophages in Mtb. However, the regulatory mechanism between lncRNAs and macrophages in tuberculosis (TB) remains unclear. In this study, we sought to investigate the effect of Mtb-associated lncRNA PCED1B-AS1 on macrophage apoptosis and autophagy. Our study first evaluated PCED1B-AS1 expression in the CD14(+) monocytes from patients with active tuberculosis and from healthy individuals. It was found that PCED1B-AS1 expression was down-regulated in patients with active tuberculosis, accompanied by significant attenuated monocyte apoptosis and enhanced autophagy. In vitro, knockdown of PCED1B-AS1 reduced macrophage apoptosis and promoted autophagy. PCED1B-AS1 serves as an endogenous sponge to block miR-155 expression in macrophages by directly binding to miR-155. Furthermore, we demonstrated that overexpression of FOXO3/Rheb, target genes of miR-155, reversed the PCED1B-AS1-mediated effects on macrophage apoptosis and autophagy. Altogether, our data indicate that PCED1B-AS1 modulates macrophage apoptosis and autophagy by targeting the miR-155 axis in active TB. (C) 2019 Elsevier Inc. All rights reserved.