Demonstrated that lncRNA SNHG16 inhibits intracellular Mycobacterium tuberculosis growth through cathelicidin pathway activation, autophagy enhancement, and effector cytokine production. Reveals a non-coding RNA regulatory mechanism in antimicrobial defense against TB.
Abstract
Long noncoding small nucleolar RNA (LncRNA) host gene 16 (SNHG16) is associated with certain diseases, including cancers. However, its role and mechanism in() infection remain unclear. Here, we demonstrated that SNHG16 expression levels were suppressed in peripheral blood mononuclear cells (PBMCs) and CD14monocytes of tuberculosis (TB) patients. SNHG16 was up-regulated by acuteinfection of PBMCs from healthy control (HC) subjects. Such TB suppression of SNHG16 was consistent with an immunosuppressive-like state driven by IL-10 signaling as seen in TB patients. Notably, SNHG16 limitedgrowth in macrophages/monocytes through autophagy and vitamin D receptor (VDR)-dependent cathelicidin (CAMP) antimicrobial pathways. Concurrently, SNHG16 was highly expressed in lymphocytes, including CD8and Vγ2 Vδ2 T-cell subsets in HCs. SNHG16 overexpression in lymphocytes allowed them to controlinfection in macrophages, and SNHG16 epigenetically increased the expression of anti-effector cytokines in lymphocytes by developing more accessible chromatin states in gene loci encoding IFN-γ, TNF-α, and Granzyme B. Furthermore, the adoptive transfer of SNHG16-overexpressing human PBMCs into-infected SCID mice conferred protective immunity againstinfection. Thus, SNHG16 drove the induction of pleiotropic effector functions that inhibited intracellulargrowth in vitro and in vivo, serving as an immunotherapy target in TB.