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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The steroid hormone ecdysone, acting through its nuclear receptor (EcR), is a key regulator of insect development and reproduction and also contributes to immune regulation and gut microbiota homeostasis. In sand flies, both immunity and the gut microbiota are critical determinants for\n                      <jats:italic>Leishmania<\/jats:italic>\n                      establishment in the midgut.\n                      <jats:italic>Phlebotomus perniciosus<\/jats:italic>\n                      is the principal vector of\n                      <jats:italic>Leishmania infantum<\/jats:italic>\n                      in the western Mediterranean basin; however, the mechanisms affecting interactions among parasite, vector immune system, and resident microbiota remain poorly understood in this species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using RNA interference\u2013mediated silencing of EcR, we assessed how disruption of ecdysone signaling affects vector immunity, gut bacteria, and parasite development. Double-stranded RNA targeting EcR or a control sequence was microinjected into\n                      <jats:italic>L. infantum<\/jats:italic>\n                      \u2013infected females, and gene expression was analyzed by RT-qPCR. Parasite load was quantified via\n                      <jats:italic>Leishmania<\/jats:italic>\n                      actin expression, while gut bacterial relative abundance was assessed using universal 16S rRNA primers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>L. infantum<\/jats:italic>\n                      infection induced expression of the sand fly ecdysone signaling\u2013related genes, immune pathway transcription factors, and antimicrobial peptides (AMPs), while significantly reducing gut bacterial load during the late phase of parasite infection. In contrast, EcR silencing suppressed downstream ecdysone-related genes, impaired activation of the immune deficiency (Imd) and JAK\/STAT pathways, and disrupted AMPs expression. This was associated with a marked increase in bacterial relative abundance in sugar-fed sand flies and altered microbial and parasite loads in\n                      <jats:italic>Leishmania<\/jats:italic>\n                      -infected sand flies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Collectively, our results indicate that ecdysone signaling regulates the Imd and JAK\/STAT transcription factors, thereby modulating\n                      <jats:italic>P. perniciosus<\/jats:italic>\n                      immune responses and suppressing the gut microbiota. Disruption of ecdysone signaling reveals an inverse correlation between parasite burden and bacterial abundance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings identify ecdysone signaling as a central regulator coordinating immune responses and maintaining the balance between\n                      <jats:italic>Leishmania<\/jats:italic>\n                      and the gut microbiota in sand flies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1904500","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:40:53Z","timestamp":1786426853000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ecdysone signaling acts as a regulator of immunity and microbiota balance, 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