Allatostatin C modulates nociception and immunity in Drosophila.

Abstract

Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play during pathogenic bacterial infection. After bacterial infection, we found robust upregulation of ligand-gated ion channels and allatostatin receptors involved in nociception, which potentially leads to hyperalgesia. We further found that Allatostatin-C Receptor 2 (AstC-R2) plays a crucial role in host survival during infection with the pathogenic bacterium Photorhabdus luminescens. Upon examination of immune signaling in AstC-R2 deficient mutants, we demonstrated that Allatostatin-C Receptor 2 specifically inhibits the Immune deficiency pathway, and knockdown of AstC-R2 leads to overproduction of antimicrobial peptides related to this pathway and decreased host survival. This study provides mechanistic insights into the importance of microbe-nociceptor interactions during bacterial challenge. We posit that Allatostatin C is an immunosuppressive substance released by nociceptors or Drosophila hemocytes that dampens IMD signaling in order to either prevent immunopathology or to reduce unnecessary metabolic cost after microbial stimulation. AstC-R2 also acts to dampen thermal nociception in the absence of infection, suggesting an intrinsic neuronal role in mediating these processes during homeostatic conditions. Further examination into the signaling mechanisms by which Allatostatin-C alters immunity and nociception in Drosophila may reveal conserved pathways which can be utilized towards therapeutically targeting inflammatory pain and chronic inflammation.

• Authors: Nathaniel D Bachtel, Gary A Hovsepian, Douglas F Nixon, Ioannis Eleftherianos
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 7501 (05 14 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29760446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimicrobial Cationic Peptides
• AstC-R2 protein, Drosophila
• Blood Proteins
• Drosophila Proteins
• Ion Channels
• Neuropeptides
• Receptors, G-Protein-Coupled
• TrpA1 protein, Drosophila
• cationic antimicrobial protein 57, human
• allatostatin

Topics

• Animals
• Antimicrobial Cationic Peptides (metabolism)
• Bacterial Infections (complications, drug therapy, immunology, veterinary)
• Blood Proteins (metabolism)
• Disease Models, Animal
• Drosophila Proteins (deficiency, genetics)
• Drosophila melanogaster
• Female
• Gene Knockdown Techniques
• Hot Temperature
• Hyperalgesia (drug therapy, immunology, microbiology, veterinary)
• Immunity (drug effects)
• Ion Channels (genetics)
• Mutation
• Neuropeptides (pharmacology)
• Nociception (drug effects)
• Photorhabdus (immunology, pathogenicity)
• Receptors, G-Protein-Coupled (deficiency, genetics)
• Up-Regulation (drug effects)