Liver Immune Cells Release Type 1 Interferon Due to DNA Sensing and Amplify Liver Injury from Acetaminophen Overdose

Alan Moreira de Araujo; Maísa Mota Antunes; Matheus Silvério Mattos; Ariane Barros Diniz; Débora Moreira Alvarenga; Brenda Naemi Nakagaki; Érika de Carvalho; Viviane Aparecida Souza Lacerda; Raquel Carvalho-Gontijo; Jorge Goulart; Kassiana Mafra; Maria Alice Freitas-Lopes; Hortência Maciel de Castro Oliveira; Camila Miranda Dutra; Bruna Araújo David; Aristóbolo Mendes Silva; Valerie Quesniaux; Bernhard Ryffel; Sergio Costa Oliveira; Glen N Barber; Daniel Santos Mansur; Thiago Mattar Cunha; Rafael Machado Rezende; André Gustavo Oliveira; Gustavo Batista Menezes

doi:10.3390/cells7080088

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Liver Immune Cells Release Type 1 Interferon Due to DNA Sensing and Amplify Liver Injury from Acetaminophen Overdose

Journal article

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Peer reviewed

Liver Immune Cells Release Type 1 Interferon Due to DNA Sensing and Amplify Liver Injury from Acetaminophen Overdose

Alan Moreira de Araujo, Maísa Mota Antunes, Matheus Silvério Mattos, Ariane Barros Diniz, Débora Moreira Alvarenga, Brenda Naemi Nakagaki, Érika de Carvalho, Viviane Aparecida Souza Lacerda, Raquel Carvalho-Gontijo, Jorge Goulart, …

Cells (Basel, Switzerland), Vol.7(8), p.88

2018-07-27

DOI: https://doi.org/10.3390/cells7080088

PMCID: PMC6115735

PMID: 30060463

Abstract

hepatology

immune system

in vivo imaging

immunity

DNA sensing

Hepatocytes may rupture after a drug overdose, and their intracellular contents act as damage-associated molecular patterns (DAMPs) that lead to additional leukocyte infiltration, amplifying the original injury. Necrosis-derived DNA can be recognized as a DAMP, activating liver non-parenchymal cells (NPCs). We hypothesized that NPCs react to DNA by releasing interferon (IFN)-1, which amplifies acetaminophen (APAP)-triggered liver necrosis. We orally overdosed different knockout mouse strains to investigate the pathways involved in DNA-mediated amplification of APAP-induced necrosis. Mice were imaged under intravital confocal microscopy to estimate injury progression, and hepatocytes and liver NPCs were differentially isolated for gene expression assays. Flow cytometry (FACS) using a fluorescent reporter mouse estimated the interferon-beta production by liver leukocytes under different injury conditions. We also treated mice with DNase to investigate the role of necrosis DNA signaling in IFN-1 production. Hepatocytes released a large amount of DNA after APAP overdose, which was not primarily sensed by these cells. However, liver NPCs promptly sensed such environmental disturbances and activated several DNA sensing pathways. Liver NPCs synthesized and released IFN-1, which was associated with concomitant hepatocyte necrosis. Ablation of IFN-1 recognition in interferon α/β receptor (IFNAR ) mice delayed APAP-mediated liver necrosis and dampened IFN-1 sensing pathways. We demonstrated a novel loop involving DNA recognition by hepatic NPCs and additional IFN-1 mediated hepatocyte death.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.609 Toll-like Receptors
Web Of Science research areas: Cell Biology
ESI research areas: Biology & Biochemistry

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Title: Liver Immune Cells Release Type 1 Interferon Due to DNA Sensing and Amplify Liver Injury from Acetaminophen Overdose
Creators: Alan Moreira de Araujo - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. amoreiradearaujo@gmail.com
Maísa Mota Antunes - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. maisaantunes@gmail.com
Matheus Silvério Mattos - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. mattosms@yahoo.com.br
Ariane Barros Diniz - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. abarrosdiniz@gmail.com
Débora Moreira Alvarenga - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. deboraalvarenga@yahoo.com
Brenda Naemi Nakagaki - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. brendanaemi22@gmail.com
Érika de Carvalho - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. erikacarvalhobio@gmail.com
Viviane Aparecida Souza Lacerda - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. viviane_lacerda@outlook.com
Raquel Carvalho-Gontijo - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. rakel.cg@gmail.com
Jorge Goulart - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. jorge.ferreira@cpqrr.fiocruz.br
Kassiana Mafra - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. kassiana93@gmail.com
Maria Alice Freitas-Lopes - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. licefl95@gmail.com
Hortência Maciel de Castro Oliveira - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. hortsmaciel@gmail.com
Camila Miranda Dutra - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. camiladutra_mm@hotmail.com
Bruna Araújo David - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. brunaraujodavid@gmail.com
Aristóbolo Mendes Silva - Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. aristobolosilva@gmail.com
Valerie Quesniaux - Experimental and Molecular Immunology and Neurogenetics CNRS, University of Orleans, 45000 Orleans, France. quesniaux@cnrs-orleans.fr
Bernhard Ryffel - Experimental and Molecular Immunology and Neurogenetics CNRS, University of Orleans, 45000 Orleans, France. bernhard.ryffel@cnrs-orleans.fr
Sergio Costa Oliveira - Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. scozeus1@gmail.com
Glen N Barber - Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA. gbarber@med.miami.edu
Daniel Santos Mansur - Laboratory of Immunobiology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil. mansurds@gmail.com
Thiago Mattar Cunha - Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo 14049-900, Brazil. thicunha@usp.br
Rafael Machado Rezende - Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. rmachadorezende@bwh.harvard.edu
André Gustavo Oliveira - Departamento de Fisiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil. agoufmg@gmail.com
Gustavo Batista Menezes - Center for Gastrointestinal Biology, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627-Belo Horizonte, Minas Gerais 31270-901, Brazil. menezesgb@ufmg.br
Publication Details: Cells (Basel, Switzerland), Vol.7(8), p.88
Publisher: Switzerland
Grant note: R01 AI079336 / NIAID NIH HHS R01 CA194404 / NCI NIH HHS
Academic Unit: Leadership Department; Miller School of Medicine; Cell Biology Research
Language: English
Resource Type: Journal article
PMID: 30060463
PMCID: PMC6115735
Record Identifier: 991031560676302976