Osa-Containing Brahma Complex Regulates Innate Immunity and the Expression of Metabolic Genes in Drosophila

Abstract

Negative regulation of innate immunity is essential to avoid autoinflammation. In Drosophila melanogaster, NF-κB signaling–mediated immune responses are negatively regulated at multiple levels. Using a Drosophila RNA interference in vitro screen, we identified a set of genes inhibiting immune activation. Four of these genes encode members of the chromatin remodeling Osa-containing Brahma (BAP) complex. Silencing additional two genes of the BAP complex was shown to have the same phenotype, confirming its role in immune regulation in vitro. In vivo, the knockdown of osa and brahma was shown to enhance the expression of the Toll pathway–mediated antimicrobial peptides when the flies were challenged with Gram-positive bacteria Micrococcus luteus. In this setting, osa knockdown had a particularly strong effect on immune effectors that are predominantly activated by the Imd pathway. Accordingly, Drosophila NF-κB Relish expression was increased by osa silencing. These transcriptional changes were associated with enhanced survival from M. luteus + E. faecalis infection. Besides regulating the expression of immune effector genes, osa RNA interference decreased the expression of a large group of genes involved in metabolism, particularly proteolysis. Of note, the expression of the recently characterized, immune-inducible gene Induced by Infection (IBIN) was diminished in osa knockdown flies. Although IBIN has been shown to modulate metabolism upon infection, the expression of selected Osa-regulated metabolism genes was not rescued by overexpressing IBIN. We conclude that the BAP complex regulates expression of genes involved in metabolism at least partially independent or downstream of IBIN. Moreover, Osa affects the NF-κB–mediated immune response by regulating Drosophila NF-κB factor Relish expression.