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Using a murine model with therapeutically relevant dosing, the study tests prophylactic levofloxacin on immune outcomes. Results show heightened iNOS expression in shorter-lived interstitial and TIM4-CD4+ macrophage subsets, reduced in microbially rich colon, and direct effects on developing bone-marrow macrophages. Mitochondrial hyperpolarization supports fluoroquinolone-specific, off-target modulation of macrophage immunity, with similar findings for ciprofloxacin but not doxycycline. Concludes that antibiotic choice should consider tissue-specific prophylactic impacts.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fluoroquinolones-directly-drive-mitochondrial-hyperpolarization-and-modulate-inos-expression-in-monocyte-derived-macrophage-populations-study-abstract/443649/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/fluoroquinolones-directly-drive-mitochondrial-hyperpolarization-and-modulate-inos-expression-in-monocyte-derived-macrophage-populations-study-abstract/443649.png","ImageObject",300,407,{"name":92,"@type":93},"Jacob","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address about fluoroquinolones?","Question",{"text":112,"@type":113},"How prophylactic fluoroquinolone treatment alters innate immunity beyond their bactericidal activity, focusing on macrophage functions and iNOS expression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which immune marker and macrophage subsets change after levofloxacin treatment?",{"text":117,"@type":113},"The study reports heightened iNOS expression specifically in shorter-lived CD206− interstitial macrophages and in the shorter-lived TIM4−CD4+ population within the large intestine.",{"name":119,"@type":110,"acceptedAnswer":120},"How does levofloxacin directly affect macrophages according to the mechanistic experiments?",{"text":121,"@type":113},"Bone-marrow-derived macrophages show that levofloxacin directly drives iNOS expression and increases phagocytosis when present during developing macrophage stages, and the effect is linked to mitochondrial hyperpolarization, indicating off-target immune modulation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},443649,1791694856,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962084931830,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Research Article  \nFluoroquinolones directly drive mitochondrial hyperpolarization and modulate iNOS expression in monocyte-derived macrophage populations  \nAlexander W. Hardgrave1,†, Megan Dooley 1,†, Ivy Maminimini 1, Adura Faniyi 1,  \nAntonia Christodoulidou 1, Yasmine Alshammari 1,2, Helen J. March3, Riccardo V. D’Elia4,5, * and John J. Worthington 1, *,  \n1Faculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, Lancaster, UK 2Faculty of Allied Health Sciences, Department of Medical Laboratory Sciences, Kuwait University, Kuwait City, Kuwait  \n3 Pharmacy Department, Royal Oldham Hospital, Northern Care Alliance NHS Trust, Oldham, UK 4CBR Division, Defence Science and Technology Laboratory Porton Down, Salisbury, UK 5Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK †Co-first author  \n*Corresponding authors. Riccardo V. D’Elia, CBR Division, Defence Science and Technology Laboratory Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK. Email: [rvdelia@mail.dstl.gov.uk](rvdelia@mail.dstl.gov.uk); John J. Worthington, Faculty of Health and Medicine, Department of Biomedical and Life Sciences, University of Lancaster, B26 Furness Building, Bailrigg, Lancaster, LA1 4YG, UK. E-mail: [j.j.worthington@lancaster.ac.uk](j.j.worthington@lancaster.ac.uk).  \nAbstract  \nIntroduction: The fluoroquinolone levofloxacin is often selected for use prophylactically as well as during respiratory infections. However, studies on how these antibiotics may alter innate immunity, as opposed to their bactericidal activity, are limited.  \nMaterials & Methods: We employed a murine model of therapeutically relevant antibiotic dosing to investigate the effect of prophylactic levofloxacin treatment on innate immunity.  \nResults: We observed mild pathology at the barrier sites of both the lung and colon in terms of alveolar space and goblet cell numbers, respectively. Although we saw no alteration in lung immune populations of neutrophils, eosinophils, or dendritic cells, we did see heightened expression of macrophage inducible nitric oxide synthase (iNOS) . Interestingly this was only present in the shorter-lived CD206 − interstitial macrophage subset and not observed in the long-lived resident alveolar population. Within the large intestine levofloxacin also targeted iNOS expression in the shorter-lived TIM4-CD4+ population but conversely inhibiting expression in the microbially rich colon. We therefore utilized the bone marrow-derived macrophage system, devoid of microbial interactions and demonstrated that levofloxacin had a direct effect on driving iNOS expression and increasing phagocytosis but only when present in developing macrophages and not mature macrophage populations. Our macrophage observations were replicated in ciprofloxacin, but not doxycycline-treated animals, indicating a fluoroquinolone specific action. Mechanistically, fluoroquinolone treatment was associated with mitochondrial hyperpolarization, indicating a direct alteration of macrophage immunity via off target effects.  \nConclusion: Collectively, this study demonstrates a direct action of fluoroquinolones on macrophage immunity, which should be considered when selecting antibiotics for tissue specific and prophylactic use.  \nKeywords: macrophage, lung, mucosal immunology, antibiotics, mitochondria  \nReceived 9 June 2025; revised 26 September 2025; accepted 11 October 2025  \n© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society of Immunology.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.  \nGraphical Abstract  \nIntroduction  \nThe lung must balance the efficient exchange of oxygen and ca","cbCaireGCTk5ulQb","https://ap.wps.com/l/cbCaireGCTk5ulQb","pdf",1359746,14,"English","# Introduction\n## Antibiotics and off-target effects on immunity\n## Role of macrophages in respiratory infection\n# Results\n## Mild pathology at lung and colon barrier sites\n## Subset-specific modulation of iNOS expression\n## Developmental-stage dependence and antibiotic specificity\n## Mechanistic link to mitochondrial hyperpolarization\n# Conclusion","[{\"question\":\"What question does the study address about fluoroquinolones?\",\"answer\":\"How prophylactic fluoroquinolone treatment alters innate immunity beyond their bactericidal activity, focusing on macrophage functions and iNOS expression.\"},{\"question\":\"Which immune marker and macrophage subsets change after levofloxacin treatment?\",\"answer\":\"The study reports heightened iNOS expression specifically in shorter-lived CD206− interstitial macrophages and in the shorter-lived TIM4−CD4+ population within the large intestine.\"},{\"question\":\"How does levofloxacin directly affect macrophages according to the mechanistic experiments?\",\"answer\":\"Bone-marrow-derived macrophages show that levofloxacin directly drives iNOS expression and increases phagocytosis when present during developing macrophage stages, and the effect is linked to mitochondrial hyperpolarization, indicating off-target immune modulation.\"}]","Fluoroquinolones directly drive mitochondrial hyperpolarization and modulate iNOS expression in monocyte-derived macrophage populations - Study abstract | PDF",1790704780,35]