{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:01:04Z","timestamp":1790319664194,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The immune response to bacterial infection demonstrates circadian rhythmicity, with heightened antibacterial immunity often observed during the daytime. This circadian\u2010gated immune response is believed to have evolved to synchronize peak antibacterial immunity with the increased threat of infection when active. Using a larval zebrafish infection model, we have previously shown that light has a positive effect on antibacterial immunity, with enhanced survival and neutrophil recruitment observed when infections are delivered during the light phase. However, the specific contribution of the light\u2010detecting pineal gland and its principal hormone, melatonin, to this circadian immune response has not been investigated. Here, we examined whether the pineal gland modulates the host response to bacterial infection in a time\u2010of\u2010day\u2013dependent manner by targeted ablation of the pineal gland. To generate pineal gland\u2010deficient larvae we created the transgenic zebrafish line\n                    <jats:italic>Tg(exorh:YFP\u2010NTR2.0)<\/jats:italic>\n                    that restricts expression of the highly efficient nitroreductase variant NTR2.0 to pinealocytes, enabling metronidazole\u2010mediated pinealectomy. We also analyzed larvae lacking the\n                    <jats:italic>brain\u2010specific homeobox<\/jats:italic>\n                    (\n                    <jats:italic>bsx<\/jats:italic>\n                    ) gene, that encodes a transcription factor essential for pineal gland development. Both approaches resulted in complete loss of the pineal gland, confirmed by live imaging, the absence of\n                    <jats:italic>arylalkylamine N\u2010acetyltransferase 2<\/jats:italic>\n                    (\n                    <jats:italic>aanat2<\/jats:italic>\n                    ) expression and diminished melatonin production. Pineal gland\u2010deficient larvae exhibited normal survival and neutrophil recruitment when infected during the light phase, indicating that daytime immune defenses can be maintained independently of the pineal gland. In contrast, infection of pineal gland\u2010deficient larvae during the dark phase led to significantly reduced survival, which correlated with impaired neutrophil recruitment to the infection site. These findings demonstrate that the pineal gland plays an important role in supporting nighttime antibacterial immunity in larval zebrafish.\n                  <\/jats:p>","DOI":"10.1111\/jpi.70179","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:12:22Z","timestamp":1787037142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Pineal Gland Is Required for Optimal Nighttime Immunity to Bacterial Infection in Larval Zebrafish"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5702-8789","authenticated-orcid":false,"given":"Gabriel","family":"Anasarias\u2010Dumo","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8564-8508","authenticated-orcid":false,"given":"Yevetta Y.","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2685-4779","authenticated-orcid":false,"given":"David","family":"Cumin","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5590-1808","authenticated-orcid":false,"given":"James F.","family":"Cheeseman","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9064-3090","authenticated-orcid":false,"given":"Guy R.","family":"Warman","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3554-0133","authenticated-orcid":false,"given":"Jonathan W.","family":"Astin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences The University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6473-7720","authenticated-orcid":false,"given":"Christopher J.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences The University of Auckland Auckland New 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