{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:04:50Z","timestamp":1791453890172,"version":"4.3.3"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,7,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Emergency granulopoiesis is a hematopoietic program of stem cell-driven neutrophil production used to counteract immune cell exhaustion following infection.\n            <jats:named-content content-type=\"genus-species\">Shigella flexneri<\/jats:named-content>\n            is a Gram-negative enteroinvasive pathogen controlled by neutrophils. In this study, we use a\n            <jats:italic>Shigella<\/jats:italic>\n            -zebrafish (\n            <jats:named-content content-type=\"genus-species\">Danio rerio<\/jats:named-content>\n            ) infection model to investigate emergency granulopoiesis\n            <jats:italic>in vivo<\/jats:italic>\n            . We show that stem cell-driven neutrophil production occurs in response to\n            <jats:italic>Shigella<\/jats:italic>\n            infection and requires macrophage-independent signaling by granulocyte colony-stimulating factor (Gcsf). To test whether emergency granulopoiesis can function beyond homoeostasis to enhance innate immunity, we developed a reinfection assay using zebrafish larvae that have not yet developed an adaptive immune system. Strikingly, larvae primed with a sublethal dose of\n            <jats:italic>Shigella<\/jats:italic>\n            are protected against a secondary lethal dose of\n            <jats:italic>Shigella<\/jats:italic>\n            in a type III secretion system (T3SS)-dependent manner. Collectively, these results highlight a new role for emergency granulopoiesis in boosting host defense and demonstrate that zebrafish larvae can be a valuable\n            <jats:italic>in vivo<\/jats:italic>\n            model to investigate innate immune memory.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:italic>Shigella<\/jats:italic>\n            is an important human pathogen of the gut. Emergency granulopoiesis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells (HSPCs) upon infection and is widely considered a homoeostatic mechanism for replacing exhausted leukocytes. In this study, we developed a\n            <jats:italic>Shigella<\/jats:italic>\n            -zebrafish infection model to investigate stem cell-driven emergency granulopoiesis. We discovered that zebrafish initiate granulopoiesis in response to\n            <jats:italic>Shigella<\/jats:italic>\n            infection, via macrophage-independent signaling of granulocyte colony-stimulating factor (Gcsf). Strikingly, larvae primed with a sublethal dose of\n            <jats:italic>Shigella<\/jats:italic>\n            are protected against a secondary lethal dose of\n            <jats:italic>Shigella<\/jats:italic>\n            in a type III secretion system (T3SS)-dependent manner. Taken together, we show that zebrafish infection can be used to capture\n            <jats:italic>Shigella<\/jats:italic>\n            -mediated stem cell-driven granulopoiesis and provide a new model system to study stem cell biology\n            <jats:italic>in vivo<\/jats:italic>\n            . Our results also highlight the potential of manipulating stem cell-driven granulopoiesis to boost innate immunity and combat infectious disease.\n          <\/jats:p>","DOI":"10.1128\/mbio.00933-18","type":"journal-article","created":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T13:36:13Z","timestamp":1529933773000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["<i>Shigella<\/i>\n            -Induced Emergency Granulopoiesis Protects Zebrafish Larvae from Secondary Infection"],"prefix":"10.1128","volume":"9","author":[{"given":"Alexandra R.","family":"Willis","sequence":"first","affiliation":[{"name":"Section of Microbiology, MRC Centre of Molecular Bacteriology and Infection (CMBI), Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Torraca","sequence":"additional","affiliation":[{"name":"Section of Microbiology, 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