Combination of Mass Cytometry and Imaging Analysis Reveals Origin, Location, and Functional Repopulation of Liver Myeloid Cells in Mice

dc.creatorDavid, Bruna Araujo
dc.creatorRezende, Rafael Machado
dc.creatorAntunes, Maísa Mota
dc.creatorSantos, Mônica Morais
dc.creatorLopes, Maria Alice Freitas
dc.creatorDiniz, Ariane Barros
dc.creatorPereira, Rafaela Vaz Sousa
dc.creatorMarchesi, Sarah Cozzer
dc.creatorAlvarenga, Débora Moreira
dc.creatorNakagaki, Brenda Naemi
dc.creatorAraújo, Alan Moreira
dc.creatorReis, Daniela Silva dos
dc.creatorRocha, Renata Monti
dc.creatorMarques, Pedro Elias
dc.creatorLee, Woo-Yong
dc.creatorDeniset, Justin
dc.creatorLiew, Pei Xiong
dc.creatorRubino, Stephen
dc.creatorCox, Laura
dc.creatorPinho, Vanessa
dc.creatorCunha, Thiago Mattar
dc.creatorFernandes, Gabriel Rocha
dc.creatorOliveira, André Gustavo
dc.creatorTeixeira, Mauro Martins
dc.creatorKubes, Paul
dc.creatorMenezes, Gustavo Batista
dc.date2017-12-06T18:43:34Z
dc.date2017-12-06T18:43:34Z
dc.date2016
dc.date.accessioned2023-09-26T23:43:03Z
dc.date.available2023-09-26T23:43:03Z
dc.identifierDAVID, Bruna Araujo et al. Combination of Mass Cytometry and Imaging Analysis Reveals Origin, Location, and Functional Repopulation of Liver Myeloid Cells in Mice. Gastroenterology. v. 151, n. 6, p. 1176-1191, 2016
dc.identifier0016-5085
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/23531
dc.identifier10.1053/j.gastro.2016.08.024
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8893480
dc.descriptionBACKGROUND & AIMS: Resident macrophages are derived from yolk sac precursors and seed the liver during embryogenesis. Native cells may be replaced by bone marrow precursors during extensive injuries, irradiation, and infections. We investigated the liver populations of myeloid immune cells and their location, as well as the dynamics of phagocyte repopulation after full depletion. The effects on liver function due to the substitution of original phagocytes by bone marrow-derived surrogates were also examined. METHODS: We collected and analyzed liver tissues from C57BL/6 (control), LysM-EGFP, B6 ACTb-EGFP, CCR2-/-, CD11c-EYFP, CD11c-EYFP-DTR, germ-free mice, CX3CR1gfp/gfp, CX3CR1gpf/wt, and CX3CR1-DTR-EYFP. Liver nonparenchymal cells were immunophenotyped using mass cytometry and gene expression analyses. Kupffer and dendritic cells were depleted from mice by administration of clodronate, and their location and phenotype were examined using intravital microscopy and time-of-flight mass cytometry. Mice were given acetaminophen gavage or intravenous injections of fluorescently labeled Escherichia coli, blood samples were collected and analyzed, and liver function was evaluated. We assessed cytokine profiles of liver tissues using a multiplexed array. RESULTS: Using mass cytometry and gene expression analyses, we identified 2 populations of hepatic macrophages and 2 populations of monocytes. We also identified 4 populations of dendritic cells and 1 population of basophils. After selective depletion of liver phagocytes, intravascular myeloid precursors began to differentiate into macrophages and dendritic cells; dendritic cells migrated out of sinusoids, after a delay, via the chemokine CX3CL1. The cell distribution returned to normal in 2 weeks, but the repopulated livers were unable to fully respond to drug-induced injury or clear bacteria for at least 1 month. This defect was associated with increased levels of inflammatory cytokines, and dexamethasone accelerated the repopulation of liver phagocytes. CONCLUSIONS: In studies of hepatic phagocyte depletion in mice, we found that myeloid precursors can differentiate into liver macrophages and dendritic cells, which each localize to distinct tissue compartments. During replenishment, macrophages acquire the ability to respond appropriately to hepatic injury and to remove bacteria from the blood stream.
dc.description2021-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier Inc.
dc.rightsopen access
dc.subjectCyTOF
dc.subjectDC
dc.subjectCyTOF
dc.subjectDC
dc.subjectLiver Development
dc.subjectMouse Model
dc.titleCombination of Mass Cytometry and Imaging Analysis Reveals Origin, Location, and Functional Repopulation of Liver Myeloid Cells in Mice
dc.typeArticle


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