ショウジョウバエの幼虫は細菌感染にどう立ち向かうのか

タイトル: Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae

概要: Multiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In Drosophila melanogaster, production of reactive oxygen species (ROS) and antimicrobial peptides (AMPs) together with intestinal cell renewal play a key role in eliminating gut microbes. A complementary mechanism would be to isolate and treat pathogenic bacteria while allowing colonization by commensals. Using real-time imaging to follow the fate of ingested bacteria, we demonstrate that while commensal Lactiplantibacillus plantarum freely circulate within the intestinal lumen, pathogenic strains such as Erwinia carotovora or Bacillus thuringiensis, are blocked in the anterior midgut where they are rapidly eliminated by antimicrobial peptides. This sequestration of pathogenic bacteria in the anterior midgut requires the Duox enzyme in enterocytes, and both TrpA1 and Dh31 in enteroendocrine cells. Supplementing larval food with hCGRP, the human homolog of Dh31, is sufficient to block the bacteria, suggesting the existence of a conserved mechanism. While the IMD pathway is essential for eliminating the trapped bacteria, it is dispensable for the blockage. Genetic manipulations impairing bacterial compartmentalization result in abnormal colonization of posterior midgut regions by pathogenic bacteria. Despite a functional IMD pathway, this ectopic colonization leads to bacterial proliferation and larval death, demonstrating the critical role of bacteria anterior sequestration in larval defense. Our study reveals a temporal orchestration during which pathogenic bacteria, but not innocuous, are confined in the anterior part of the midgut in which they are eliminated in an IMD pathway dependent manner. AUTHOR SUMMARYTypically, when considering the immune response of animals to infection, we focus on classical immunity, encompassing both innate and adaptive aspects such as antimicrobials and circulating immune cells. However, a broader perspective on immunity includes additional strategies that enhance host protection, such as behavioral avoidance and internal mechanisms that restrict pathogen propagation. In our study using Drosophila larvae as a model, we uncovered spatially and temporally interconnected events that are crucial for effectively combating intestinal infections. Our findings reveal a two-step defense mechanism: first, the larvae rapidly discriminate between bacterial strains, effectively confining hazardous ones in the anterior section of the intestine. These blocked bacteria trigger the synthesis and release of antimicrobial peptides by the host, which ultimately eradicate the entrapped pathogens. Our experiments show that larvae capable of both limiting bacteria spreading and producing antimicrobial peptides withstand infections. In contrast, the absence of either one of these sequential defenses results in high mortality among the larvae, emphasizing the importance of each step and the necessity of their precise coordination in the immune response.