Insects Go on a STING Operation to Tackle Intracellular Invaders Suzana Zakovic, Elena A. Levashina  Immunity  Volume 49, Issue 2, Pages 195-197 (August 2018) DOI: 10.1016/j.immuni.2018.08.003 Copyright © 2018 Elsevier Inc. Terms and Conditions

Figure 1 Model of dSTING Signaling in Antiviral Responses Drosophila C virus (DCV) and Cricket paralysis virus (CrPV) or Listeria infections activate dSTING whose translocation from the endoplasmic reticulum activates non-canonical IKKβ-Relish module of the IMD pathway. In the canonical pathway, Relish is activated by cleavage of the inhibitory ankyrin repeat reach domain (ANK) from the signaling REL homology domain (RHD). In Bombyx mori, binding of BmCasp8L to inactive BmSTING prevents BmRelish cleavage by the caspase BmDredd. During the nuclear polyhedrosis virus (NPV) infection, BmSTING binding to cGAMP activates BmRelish by BmDredd cleavage. This mode of Relish activation by STING signaling awaits confirmation in other insects. In Drosophila, Relish RHD translocates to the nucleus and induces expression of dSTING that serves as a positive feedback loop for its expression and that of other antiviral effector genes including Nazo. In some tissues (e.g., the brain), dSTING directly inhibits Zika virus (ZIKV) replication by autophagy, whereas Nazo restricts DCV infection by an as yet unknown mechanism. Nazo is a transmembrane protein with potential residence in the endoplasmic reticulum or mitochondria, but its exact localization is unknown. Extra- and intracellular activation of the canonical IMD pathway by Listeria-derived DAP-type peptidoglycans through PGRP-LC and PGRP-LE receptors, respectively, activates the canonical IMD pathway and synthesis of AMPs. Gray color depicts activation of the canonical IMD pathway. Red arrows show the non-canonical components. Black arrows indicate the overlap between the canonical and non-canonical IMD signaling. Immunity 2018 49, 195-197DOI: (10.1016/j.immuni.2018.08.003) Copyright © 2018 Elsevier Inc. Terms and Conditions