Unfolded Protein Response Genes Regulated by CED-1 Are Required for Caenorhabditis Elegans Innate Immunity

Abstract

<p>The first line of defense against pathogens is the phylogenetically ancient innate immune system. This system consists of physical barriers and conserved signaling pathways are activated upon infection to produce effector molecules that mount a microbicidal response. Recently, <em>C. elegans</em> has been established as a model organism for the study of innate immunity due to <em>C. elegans</em> genetic tractability and origins predating the evolution of adaptive immunity. Conserved defense pathways essential for mammalian innate immunity have been identified in <em>C. elegans</em>. However, most receptors critical for the activation of the defense signaling pathways in <em>C. elegans</em> remain unknown. The goal of this work was to study CED-1 and its potential role as a cell-surface signaling receptor essential for <em>C. elegans</em> immune response. In this study, we performed a full-genome microarray analysis and discovered that CED-1 functions to activate the expression of <em>pqn/abu</em> unfolded protein response (UPR) genes. The unfolded protein response has been implicated in the normal physiology of immune defense and in several disorders including diabetes, cancer, and neurodegenerative disease. Here we show that <em>ced-1</em> and <em>pqn/abu</em> genes are required for the survival of <em>C. elegans</em> exposed to live <em>S. enterica</em>. We also show that the overexpression of <em>pqn/abu</em> genes confers protection to pathogen-mediated killing. Taken together, these results indicate that the apoptotic receptor CED-1 and a network of PQN/ABU proteins involved in a non-canonical UPR response are required for proper defense to pathogen infection in <em>Caenorhabditis elegans</em>.</p>