Priming of microvascular endothelium by microbiota-derived metabolites regulates neutrophil trafficking to the liver during sepsis
| Autor: | Amanda Zucoloto, Katrina Yu, Kathy McCoy, Braedon McDonald |
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| Rok vydání: | 2021 |
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| Zdroj: | The Journal of Immunology. 206:112.09-112.09 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.206.supp.112.09 |
| Popis: | During systemic bacterial infections and sepsis, neutrophils are recruited en mass into the microcirculation of the liver and lungs as part of a coordinated intravascular response to defend the bloodstream against bacterial pathogens. The mechanisms that program this response have not been elucidated. The gut microbiota regulates immune cell development and function. In extra-intestinal organs, the microbiota conducts long-distance communication with immune cells through the release of metabolites into the bloodstream. While gut microbes augment granulopoiesis in the bone marrow, the role the microbiota and commensal-derived metabolites on neutrophil trafficking is poorly understood. Using confocal intravital microscopy, we observed that germ-free (GF) mice had impaired neutrophil recruitment to the liver, but not the lungs, during sepsis. Analysis of microbial metabolites in the gut, portal circulation (between gut and liver), and systemic circulation revealed that commensal-derived D-lactate levels are high in the gut and portal circulation, but nearly absent in the systemic circulation. Reconstitution of gut-to-liver D-lactate signalling by enteral administration restored neutrophil trafficking to the liver. In contrast, D-lactate did not impact neutrophil infiltration to the lungs, systemic levels of pro-inflammatory mediators or granulopoiesis. Instead, commensal D-lactate primed liver endothelium to express adhesion molecules required for neutrophil adhesion and crawling. Taken together, we show that compartmentalized molecular communication between gut microbes and the liver primes the microvascular endothelium for neutrophil recruitment in response to systemic bacterial infection and sepsis. |
| Databáze: | OpenAIRE |
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