{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:56:52Z","timestamp":1785466612479,"version":"3.56.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001664","name":"Leibniz-Gemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Octopamine, the functional equivalent of noradrenaline in invertebrates, is a key neuromodulator that also influences immune functions. However, the receptor\u2011specific roles of octopamine in regulating innate immunity in\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                      remain incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using loss\u2011of\u2011function mutants for the two major octopamine receptors Oct\u03b21R and Oct\u03b22R, combined with systemic bacterial infection models, bacterial clearance assays, in vivo and in vitro phagocytosis assays, and quantification of antimicrobial peptide (AMP) gene expression, we dissected the contribution of each receptor to distinct immune effector modules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Flies deficient in Oct\u03b21R or Oct\u03b22R exhibited reduced survival and impaired bacterial clearance following systemic infection, which was associated with increased bacterial persistence. This phenotype correlated with reduced phagocytic activity of hemocytes in both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays. In contrast, deficiency of Oct\u03b21R or Oct\u03b22R led to enhanced induction of a subset of essential AMP genes upon infection, indicating that octopamine signaling dampens specific humoral immune outputs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data demonstrate that octopamine exerts a decisive influence on the performance of the Drosophila innate immune system by differentially modulating cellular (phagocytosis) and humoral (AMP expression) immune modules in a receptor\u2011specific manner. These findings establish octopaminergic signaling through Oct\u03b21R and Oct\u03b22R as an important node of neuro\u2011immune regulation in invertebrates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1720126","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T05:11:32Z","timestamp":1767849092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Octopamine modulates the innate immune response in Drosophila melanogaster"],"prefix":"10.3389","volume":"16","author":[{"given":"Karin","family":"Uliczka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Papenmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"H\u00f6schler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Roeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Heine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1992.03480090092034","article-title":"The concepts of stress and stress system disorders. 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