Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/23531
Title: Combination of Mass Cytometry and Imaging Analysis Reveals Origin, Location, and Functional Repopulation of Liver Myeloid Cells in Mice
Authors: David, Bruna Araujo
Rezende, Rafael Machado
Antunes, Maísa Mota
Santos, Mônica Morais
Lopes, Maria Alice Freitas
Diniz, Ariane Barros
Pereira, Rafaela Vaz Sousa
Marchesi, Sarah Cozzer
Alvarenga, Débora Moreira
Nakagaki, Brenda Naemi
Araújo, Alan Moreira
Reis, Daniela Silva dos
Rocha, Renata Monti
Marques, Pedro Elias
Lee, Woo-Yong
Deniset, Justin
Liew, Pei Xiong
Rubino, Stephen
Cox, Laura
Pinho, Vanessa
Cunha, Thiago Mattar
Fernandes, Gabriel Rocha
Oliveira, André Gustavo
Teixeira, Mauro Martins
Kubes, Paul
Menezes, Gustavo Batista
Affilliation: Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Harvard Medical School, Brigham and Women’s Hospital. Ann Romney Center for Neurologic Diseases. Boston, MA, United States of America.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil
University of Calgary. Alberta, Canada
University of Calgary. Alberta, Canada
University of Calgary. Alberta, Canada
Harvard Medical School, Brigham and Women’s Hospital. Ann Romney Center for Neurologic Diseases. Boston, MA, United States of America.
Harvard Medical School, Brigham and Women’s Hospital. Ann Romney Center for Neurologic Diseases. Boston, MA, United States of America.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Resolução de Inflamação. Belo Horizonte, MG, Brazil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. São Paulo, SP, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil
University of Calgary. Alberta, Canada
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil
Abstract: BACKGROUND & 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.
Keywords: CyTOF
DC
Liver Development
Mouse Model
keywords: CyTOF
DC
Issue Date: 2016
Publisher: Elsevier Inc.
Citation: DAVID, 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
DOI: 10.1053/j.gastro.2016.08.024
ISSN: 0016-5085
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos



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