Title | Shigella-Induced Emergency Granulopoiesis Protects Zebrafish Larvae from Secondary Infection |
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Type | Journal article |
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Authors | Willis, Alexandra R., Torraca, V., Gomes, Margarida C., Shelley, Jennifer, Mazon-Moya, Maria, Filloux, Alain, Lo Celso, Cristina and Mostowy, Serge |
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Abstract | Emergency granulopoiesis is a hematopoietic program of stem cell-driven neutrophil production used to counteract immune cell exhaustion following infection. Shigella flexneri is a Gram-negative enteroinvasive pathogen controlled by neutrophils. In this study, we use a Shigella-zebrafish (Danio rerio) infection model to investigate emergency granulopoiesis in vivo. We show that stem cell-driven neutrophil production occurs in response to Shigella 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 Shigella are protected against a secondary lethal dose of Shigella 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 in vivo model to investigate innate immune memory. |
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Article number | e00933-18 |
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Journal | mBio |
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Journal citation | 9 (3) |
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ISSN | 2150-7511 |
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Year | 2018 |
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Publisher | American Society for Microbiology |
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Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.1128/mbio.00933-18 |
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Publication dates |
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Published | 26 Jun 2018 |
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