Biology subjects

Royet, J.

Publications and source records attributed to Royet, J..

7 recordsLinked to original sources

bioRxiv2025

Multisensory pathogen detection drives rapid escape and shapes host-microbe interactions in Drosophila larvae

Larvae of many insects develop immersed in decomposing substrates densely populated with microbes, yet how they detect and respond to pathogenic threats during early life remains poorly understood. Here, we show that Drosophila melanogaster larvae exhibit a previously unrecognized rapid escape behavior triggered by food contaminated with metabolically active Erwinia carotovora carotovora 15 (E. cc15), a natural bacterial pathogen of flies and plants. Stationary-phase cells fail to elicit avoidance, demonstrating that larval detection of E. cc15 depends on bacterial metabolic activity rather than on its mere presence. Using targeted genetic manipulations, we identify two chemosensory pathways required for this response: a gustatory input mediated by the aversion receptor Gr33a and an olfactory input mediated by the Or49a-Orco complex. Disrupting either pathway abolishes escape, revealing that larvae integrate complementary contact-dependent and volatile cues to evaluate microbial danger. Functionally, escape enables larvae to reach uncontaminated food and partially mitigates the developmental impact of early pathogen exposure. However, dispersing larvae also transfer viable bacteria to new substrates, indicating that this defensive response can simultaneously promote pathogen spread. Together, these findings establish the first example of a rapid, multisensory escape behavior induced by a natural pathogen in Drosophila larvae and provide a tractable model for dissecting how microbial cues guide defensive decision-making and influence pathogen dissemination.

animal behavior and cognition↗

bioRxiv2024

Drosophila's sensory responses to bacterial peptidoglycan integrates positive and negative signals

Interactions between animals, including humans, and surrounding microbes are governed by a delicate balance, crucial for survival. Animals must distinguish and respond adequately to beneficial and harmful microbes to maintain homeostasis. Recent research suggests that bacterial components such as lipopolysaccharide and peptidoglycan (PGN) influence host behavior by modulating neuronal activity. PGN detection by specific neurons can prompt infected female flies to reduce oviposition or trigger avoidance behaviors via gustatory neurons. Using behavioral assays and calcium imaging, we found that PGNs can also act as attractants, activating the sweet taste circuit in a concentration-dependent manner. Our findings demonstrate that flies integrate PGN-derived positive and negative signals to make ad hoc decisions. This dual response underlines the need for Drosophila to distinguish between different concentrations of compounds in their environment, integrating sensory data to navigate efficiently in microbe-co-inhabited environments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/626038v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@8aab21org.highwire.dtl.DTLVardef@1e90d09org.highwire.dtl.DTLVardef@156f1d4org.highwire.dtl.DTLVardef@11ed69c_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- Bacterial PGN is attractive to flies - Gr5a sweet gustatory neurons are activated by PGN - Adult PER to PGN is not directly influenced by larval life - Fly gustatory response to PGN integrates both attractive and aversive signals

animal behavior and cognition↗

bioRxiv2024

Detection of bacteria through taste receptors primes the cellular immune response

Animals use their sensory system to detect cues in their external environment, then communicate, process, and integrate these cues through the nervous system in order to elicit a specific response. Taste is an important cue used by animals to explore their external environment and can modulate various aspects of animal behavior and physiology. A major ongoing challenge for animals is to detect and respond to the presence of a variety of microbes in their environment. However, to date, the links between the sensory system and the response to pathogenic threats remain poorly understood. Here we show that Drosophila melanogaster larvae use their taste system to detect bacterial peptidoglycans in their environment and respond by modulating the activity of their cellular immune system. We show that specific PeptidoGlycan Receptor Proteins (PGRPs) act in aversive taste neurons, via a non-canonical Immune Deficiency (Imd) pathway. These PGRPs mediate signaling in taste neurons and control immune cells production in the larval hematopoietic organ, the lymph gland. Taste-mediated sensing of bacteria in larvae primes the immune system, and improves survival after infection in adult flies. These results demonstrate that sensory inputs such as taste play an important role in protecting animals from bacterial infection by providing a powerful adaptive response to potential pathogens. Overall, our findings add to the growing list of examples of crosstalk between the nervous and immune systems and provide novel and important mechanisms for linking them. One Sentence SummaryNajera Mazariegos et al. demonstrate that organisms can use taste to monitor their environment for potential immune challenges and activate their immune system if they detect bacteria.

immunology↗

bioRxiv2024

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

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.

immunology↗

bioRxiv2023

Larval microbiota primes the Drosophila adult gustatory response

The survival of animals depends, among other things, on their ability to identify threats in their surrounding environment. Senses such as olfaction, vision and taste play an essential role in sampling their living environment, including microorganisms, some of which are potentially pathogenic. This study focuses on the mechanisms of detection of bacteria by the Drosophila gustatory system. We demonstrate that the peptidoglycan (PGN) that forms the cell wall of bacteria triggers an immediate feeding aversive response when detected by the gustatory system of adult flies. Although we identify ppk23+ and Gr66a+ gustatory neurons as necessary to transduce fly response to PGN, we demonstrate that they play very different roles in the process. Time-controlled functional inactivation and in vivo calcium imaging demonstrate that while ppk23+ neurons are required in the adult flies to directly transduce PGN signal, Gr66a+ neurons must be functional in larvae to allow future adults to become PGN sensitive. Furthermore, the ability of adult flies to respond to bacterial PGN is lost when they hatch from larvae reared under axenic conditions. Recolonization of axenic larvae, but not adults, with a single bacterial species, Lactobacillus brevis, is sufficient to restore the ability of adults to respond to PGN. Our data demonstrate that the genetic and environmental characteristics of the larvae are essential to make the future adults competent to respond to certain sensory stimuli such as PGN.

animal behavior and cognition↗

bioRxiv2022

Dual mode of PGRP-LE-dependent NF-κB pathway activation in bacteria infected guts

Interactions between prokaryotes and eukaryotes require a dialogue between MAMPs and PRRs. In Drosophila, bacterial peptidoglycan is detected by PGRP receptors. While the components of the signaling cascades activated upon PGN/PGRP interactions are well characterized, little is known about the subcellular events that translate these early signaling steps into target gene transcription. Using a Drosophila enteric infection model, we show that gut-associated bacteria can induce the formation of intracellular PGRP-LE aggregates which colocalized with the early endosome marker Rab5. Combining microscopic and RNA-seq analysis, we demonstrate that RNAi inactivation of the endocytosis pathway in the Drosophila gut affects the expression of essential regulators of the NF-{kappa}B response leading not only to a disruption of the immune response locally in the gut but also at the systemic level. This work sheds new light on the involvement of the endocytosis pathway in the control of the gut response to intestinal bacterial infection Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=181 HEIGHT=200 SRC="FIGDIR/small/490610v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1ed549eorg.highwire.dtl.DTLVardef@4e5315org.highwire.dtl.DTLVardef@30b1eaorg.highwire.dtl.DTLVardef@f08401_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Bacteria-derived peptidoglycan triggers an NF-kB dependent response in Drosophila gustatory neurons

Probing the external world is essential for eukaryotes to distinguish beneficial from pathogenic microorganisms. If it is clear that this task falls to the immune cells, recent work shows that neurons can also detect microbes, although the molecules and mechanisms involved are less characterized. In Drosophila, detection of bacteria-derived peptidoglycan by pattern recognition receptor (PRR) of the PGRP family expressed in immune cells, triggers NF-{kappa}B/IMD dependent signaling. We show here that one PGRP protein, called PGRP-LB, is expressed in some probosciss bitter taste neurons. In vivo calcium imaging reveals that the PGRP/IMD pathway is cell-autonomously required in these neurons to transduce the PGN signal. We finally show that NF-{kappa}B/IMD pathway activation in bitter neurons influences fly behavior. This demonstrates that flies use the same bacterial elicitor and signaling module to sense bacterial presence via the peripheral nervous system and trigger an anti-bacterial response in immune-competent cells.

neuroscience↗