Shigella -Induced Emergency Granulopoiesis Protects Zebrafish Larvae from Secondary Infection

• Published in: mBio Vol. 9; no. 3
• Main Authors: Willis, Alexandra R, Torraca, Vincenzo, Gomes, Margarida C, Shelley, Jennifer, Mazon-Moya, Maria, Filloux, Alain, Lo Celso, Cristina, Mostowy, Serge
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 26.06.2018
• Subjects: Animals; Coinfection - immunology; Coinfection - microbiology; Coinfection - physiopathology; Disease Models, Animal; Dysentery, Bacillary - immunology; Dysentery, Bacillary - microbiology; Dysentery, Bacillary - physiopathology; Female; Humans; Larva - immunology; Larva - microbiology; Leukopoiesis; Macrophages - immunology; Male; Neutrophils - cytology; Neutrophils - immunology; Observation; Shigella flexneri - physiology; Zebrafish - immunology; Zebrafish - microbiology; stem cells; zebrafish; neutrophils; emergency granulopoiesis; Shigella
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.00933-18

Emergency granulopoiesis is a hematopoietic program of stem cell-driven neutrophil production used to counteract immune cell exhaustion following infection. is a Gram-negative enteroinvasive pathogen controlled by neutrophils. In this study, we use a -zebrafish ( ) infection model to investigate emergency granulopoiesis We show that stem cell-driven neutrophil production occurs in response to 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 are protected against a secondary lethal dose of 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 model to investigate innate immune memory. 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 -zebrafish infection model to investigate stem cell-driven emergency granulopoiesis. We discovered that zebrafish initiate granulopoiesis in response to infection, via macrophage-independent signaling of granulocyte colony-stimulating factor (Gcsf). Strikingly, larvae primed with a sublethal dose of are protected against a secondary lethal dose of in a type III secretion system (T3SS)-dependent manner. Taken together, we show that zebrafish infection can be used to capture -mediated stem cell-driven granulopoiesis and provide a new model system to study stem cell biology Our results also highlight the potential of manipulating stem cell-driven granulopoiesis to boost innate immunity and combat infectious disease.