A Mesh–Duox pathway regulates homeostasis in the insect gut

Abstract

SummaryThe metazoan gut harbors complex communities of commensal and symbiotic bacterial microbes. The quantity and quality of these microbes fluctuate dynamically in response to physiological changes. The mechanisms that hosts developed to respond to and manage such dynamic changes and maintain homeostasis remain largely unknown. Here, we identify a dual oxidase (Duox)-regulating pathway that contributes in maintaining homeostasis in the gut of both Aedes aegypti and Drosophila melanogaster. We show that a gut membrane-associated protein, named Mesh, plays an important role in controlling proliferation of gut bacteria by regulating Duox expression through an Arrestin-mediated MAPK JNK/ERK phosphorylation cascade. Expression of both Mesh and Duox is correlated with the gut bacterial microbiome that, in mosquitoes, increases dramatically soon after a blood meal. Ablation of Mesh abolishes Duox induction leading to an increase of the gut microbiome load. Our study reveals that the Mesh-mediated signaling pathway is a central homeostatic mechanism of the insect gut.

Dual oxidase: a novel therapeutic target in allergic disease

“…More recent studies also indicate alternative functions for Ce‐Duox1/BLI‐3 (the single functional NOX in C. elegans ) in intestinal host defence, which are related to its ability to activate intracellular signalling pathways involving p38 MAPK signalling and the Nrf (NF‐E2 related factor) orthologue SKN‐1, thereby augmenting resistance to invading pathogens (Hoeven et al ., ). Similar intestinal host defence functions were also described for dDUOX, one of the two NOX homologues in D. melanogaster (Ha et al ., ; Ha et al ., ; Xiao et al ., ), and Duox in zebrafish (Flores et al ., ). Furthermore, studies in D. melanogaster have revealed both positive and negative regulatory mechanisms to control Duox expression or activation, which likely serve to assure its adequate response to pathogenic bacteria while tolerating commensal bacteria (Kim and Lee, ; Xiao et al ., ).…”

Validating the potential of double-stranded RNA targeting Colorado potato beetlemeshgene in laboratory and field trials

“…Mesh is a transmembrane protein important for proper organisation of the insect midgut septate junctions and Drosophila mesh mutants show an impaired barrier function of the midgut (Izumi et al 2012). Silencing mesh by RNAi in Drosophila adults, however, does not impair gut integrity but increases gut bacterial load by regulating dual oxidase expression (Xiao et al 2017).…”

Dual oxidase geneDuoxand Toll-like receptor 3 geneTLR3in the Toll pathway suppress zoonotic pathogens through regulating the intestinal bacterial community homeostasis inHermetia illucensL.

“…Toll pathway-mutant larvae lacking AMP expression generally exert reduced resistance and lethal effects to gut infection. By contrast, Duox inactivation leads to uncontrolled of bacteria in the gut of Drosophila [14], illustrating that the immune system propagation of Duox-ROS system plays a major role in intestinal immune defense. H. Illucens has only one Duox gene in the genome.…”

“…Gut membrane-associated proteins Meshregulate Duox expression throughan arrestin-mediated MAPK/JNK/ERK phosphorylation cascade and play an important role in controlling the proliferation of gut bacteria. Expression of both Mesh and Duox is correlated with the gut bacterial microbiome[14].…”