An essential complementary role of NF-κB pathway to microbicidal oxidants in Drosophila gut immunity

Abstract

In the Drosophila gut, reactive oxygen species (ROS)‐dependent immunity is critical to host survival. This is in contrast to the NF‐κB pathway whose physiological function in the microbe‐laden epithelia has yet to be convincingly demonstrated despite playing a critical role during systemic infections. We used a novel in vivo approach to reveal the physiological role of gut NF‐κB/antimicrobial peptide (AMP) system, which has been ‘masked’ in the presence of the dominant intestinal ROS‐dependent immunity. When fed with ROS‐resistant microbes, NF‐κB pathway mutant flies, but not wild‐type flies, become highly susceptible to gut infection. This high lethality can be significantly reduced by either re‐introducing Relish expression to Relish mutants or by constitutively expressing a single AMP to the NF‐κB pathway mutants in the intestine. These results imply that the local ‘NF‐κB/AMP’ system acts as an essential ‘fail‐safe’ system, complementary to the ROS‐dependent gut immunity, during gut infection with ROS‐resistant pathogens. This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS‐dependent immunity.

The dual oxidase gene BdDuox regulates the intestinal bacterial community homeostasis of Bactrocera dorsalis

“…In contrast to the systemic response including melanization, coagulation, phagocytosis and AMP production that ensures the sterility of the body cavity and hemolymph (Buchon et al, 2013), the intestinal immune responses must tolerate the presence of the gut microbiota and dietary microorganisms while responding to and eliminating potential pathogens. Previous studies done in Drosophila have suggested that the fly's gut immune response relies mainly on two types of molecular effectors that act synergistically to restrict the growth and proliferation of invading microorganisms: the AMPs and ROS (Ryu et al, 2006;Buchon et al, 2013). Previous research has found that Imd pathway-mutant flies lacking AMP expression are usually resistant to gut infection except ROS-resistant bacteria (Ha et al, 2005;Ryu et al, 2006), and could still control the dietary yeast, S. cerevisiae.…”

“…Previous studies done in Drosophila have suggested that the fly's gut immune response relies mainly on two types of molecular effectors that act synergistically to restrict the growth and proliferation of invading microorganisms: the AMPs and ROS (Ryu et al, 2006;Buchon et al, 2013). Previous research has found that Imd pathway-mutant flies lacking AMP expression are usually resistant to gut infection except ROS-resistant bacteria (Ha et al, 2005;Ryu et al, 2006), and could still control the dietary yeast, S. cerevisiae. In contrast, the DUOX inactivation led to uncontrolled propagation of S. cerevisiae in the gut of Drosophila (Ha et al, 2009a), underlying that ROS generation system has the primordial role in the gut antimicrobial response (Ha et al, 2005(Ha et al, , 2009a.…”

Midgut immune responses induced by bacterial infection in the silkworm, Bombyx mori

“…These results imply that Glov2 and Glov3 may serve as the main intestinal defense molecules during the early infection stage. Natural gut infection also activates the IMD pathway to induce local AMP gene transcription, which plays complementary roles in combating ROS-resistant microbes (Ryu et al, 2006). In our study, at 24 h, intestinal ROS levels were relatively low after P. aeruginosa and B. bombysepticus infection (Fig.…”

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

“…P. aeruginosa [79], Vibrio cholerae [80]), have shown that the two main gut epithelial responses to microbes are the production of reactive oxygen species (ROS) by the NADPH oxidase enzyme Duox, and the production of AMPs by the Imd-Relish (NF-kB) pathway [21,75,81]. Duox activity is stimulated by uracil, a microbe-derived ligand, which is released by pathogenic bacteria and certain members of the microbiota that can become pathogenic (sometimes referred to as pathobionts) [82].…”