Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients

Detalhes bibliográficos
Autor(a) principal: Garcia, Cristiana Couto
Data de Publicação: 2018
Outros Autores: Tavares, Luciana Padua, Dias, Ana Carolina Fialho, Kehdy, Fernanda de Souza Gomes, Alvarado-Arnez, Lucia Elena, Queiroz Junior, Celso M., Galvão, Izabela, Lima, Braulio Henrique, Matos, Aline da Rocha, Gonçalves, Ana Paula de Faria, Soriani, Frederico Marianetti, Moraes, Milton Ozório, Marques, João Trindade, Siqueira, Marilda Agudo Mendonça Teixeira de, Machado, Alexandre de Magalhães Vieira, Sousa, Lirlandia Pires, Russo, Remo de Castro, Teixeira, Mauro Martins
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/28360
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.
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spelling Garcia, Cristiana CoutoTavares, Luciana PaduaDias, Ana Carolina FialhoKehdy, Fernanda de Souza GomesAlvarado-Arnez, Lucia ElenaQueiroz Junior, Celso M.Galvão, IzabelaLima, Braulio HenriqueMatos, Aline da RochaGonçalves, Ana Paula de FariaSoriani, Frederico MarianettiMoraes, Milton OzórioMarques, João TrindadeSiqueira, Marilda Agudo Mendonça Teixeira deMachado, Alexandre de Magalhães VieiraSousa, Lirlandia PiresRusso, Remo de CastroTeixeira, Mauro Martins2018-08-24T16:44:27Z2018-08-24T16:44:27Z2018GARCIA, Cristiana Couto et al. Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients. Frontiers in Immunology, v. 9, p. 1-18, 2018.1664-3224https://www.arca.fiocruz.br/handle/icict/2836010.3389/fimmu.2018.00975engFrontiers Media ASCélulas T CD8 +Gravidade da doençaCélulas assassinas naturaisNeutrófilosp38Polimorfismo de nucleotídeo únicoType-I IFNCD8+ T cellsDisease SeverityNatural killer cellsNeutrophilsp38Single-nucleotide polymorphismType-I IFNPhosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Laboratório de Imunologia e Mecânica Pulmonar. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil / UNIFRANZ. Coordinación Nacional de Investigación. La Paz, Bolivia.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade de São Paulo. Departamento de Farmacologia. Laboratório de Inflamação e Dor. Universidade de São Paulo. Ribeirão Preto, SP, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunologia de Doenças Virais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de RNA de Interferência Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunologia de Doenças Virais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Laboratório de Imunologia e Mecânica Pulmonar. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Influenza A virus (IAV) infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks) are central signaling enzymes, involved in cell growth, survival, and migration. Class IB PI3K or phosphatidyl inositol 3 kinase-gamma (PI3Kγ), mainly expressed by leukocytes, is involved in cell migration during inflammation. Here, we investigated the contribution of PI3Kγ for the inflammatory and antiviral responses to IAV. PI3Kγ knockout (KO) mice were highly susceptible to lethality following infection with influenza A/WSN/33 H1N1. In the early time points of infection, infiltration of neutrophils was higher than WT mice whereas type-I and type-III IFN expression and p38 activation were reduced in PI3Kγ KO mice resulting in higher viral loads when compared with WT mice. Blockade of p38 in WT macrophages infected with IAV reduced levels of interferon-stimulated gene 15 protein to those induced in PI3Kγ KO macrophages, suggesting that p38 is downstream of antiviral responses mediated by PI3Kγ. PI3Kγ KO-derived fibroblasts or macrophages showed reduced type-I IFN transcription and altered pro-inflammatory cytokines suggesting a cell autonomous imbalance between inflammatory and antiviral responses. Seven days after IAV infection, there were reduced infiltration of natural killer cells and CD8+ T lymphocytes, increased concentration of inflammatory cytokines in bronchoalveolar fluid, reduced numbers of resolving macrophages, and IL-10 levels in PI3Kγ KO. This imbalanced environment in PI3Kγ KO-infected mice culminated in enhanced lung neutrophil infiltration, reactive oxygen species release, and lung damage that together with the increased viral loads, contributed to higher mortality in PI3Kγ KO mice compared with WT mice. In humans, we tested the genetic association of disease severity in influenza A/H1N1pdm09-infected patients with three potentially functional PIK3CG single-nucleotide polymorphisms (SNPs), rs1129293, rs17847825, and rs2230460. We observed that SNPs rs17847825 and rs2230460 (A and T alleles, respectively) were significantly associated with protection from severe disease using the recessive model in patients infected with influenza A(H1N1)pdm09. Altogether, our results suggest that PI3Kγ is crucial in balancing antiviral and inflammatory responses to IAV infection.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/28360/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALPhosphatidyl Inositol 3 Kinase-Gamma Balances.pdfPhosphatidyl Inositol 3 Kinase-Gamma Balances.pdfapplication/pdf10035595https://www.arca.fiocruz.br/bitstream/icict/28360/2/Phosphatidyl%20Inositol%203%20Kinase-Gamma%20Balances.pdf5a61fb2c618990d4314d36db3868ee2eMD52TEXTPhosphatidyl Inositol 3 Kinase-Gamma Balances.pdf.txtPhosphatidyl Inositol 3 Kinase-Gamma Balances.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
title Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
spellingShingle Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
Garcia, Cristiana Couto
Células T CD8 +
Gravidade da doença
Células assassinas naturais
Neutrófilos
p38
Polimorfismo de nucleotídeo único
Type-I IFN
CD8+ T cells
Disease Severity
Natural killer cells
Neutrophils
p38
Single-nucleotide polymorphism
Type-I IFN
title_short Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
title_full Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
title_fullStr Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
title_full_unstemmed Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
title_sort Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients
author Garcia, Cristiana Couto
author_facet Garcia, Cristiana Couto
Tavares, Luciana Padua
Dias, Ana Carolina Fialho
Kehdy, Fernanda de Souza Gomes
Alvarado-Arnez, Lucia Elena
Queiroz Junior, Celso M.
Galvão, Izabela
Lima, Braulio Henrique
Matos, Aline da Rocha
Gonçalves, Ana Paula de Faria
Soriani, Frederico Marianetti
Moraes, Milton Ozório
Marques, João Trindade
Siqueira, Marilda Agudo Mendonça Teixeira de
Machado, Alexandre de Magalhães Vieira
Sousa, Lirlandia Pires
Russo, Remo de Castro
Teixeira, Mauro Martins
author_role author
author2 Tavares, Luciana Padua
Dias, Ana Carolina Fialho
Kehdy, Fernanda de Souza Gomes
Alvarado-Arnez, Lucia Elena
Queiroz Junior, Celso M.
Galvão, Izabela
Lima, Braulio Henrique
Matos, Aline da Rocha
Gonçalves, Ana Paula de Faria
Soriani, Frederico Marianetti
Moraes, Milton Ozório
Marques, João Trindade
Siqueira, Marilda Agudo Mendonça Teixeira de
Machado, Alexandre de Magalhães Vieira
Sousa, Lirlandia Pires
Russo, Remo de Castro
Teixeira, Mauro Martins
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Garcia, Cristiana Couto
Tavares, Luciana Padua
Dias, Ana Carolina Fialho
Kehdy, Fernanda de Souza Gomes
Alvarado-Arnez, Lucia Elena
Queiroz Junior, Celso M.
Galvão, Izabela
Lima, Braulio Henrique
Matos, Aline da Rocha
Gonçalves, Ana Paula de Faria
Soriani, Frederico Marianetti
Moraes, Milton Ozório
Marques, João Trindade
Siqueira, Marilda Agudo Mendonça Teixeira de
Machado, Alexandre de Magalhães Vieira
Sousa, Lirlandia Pires
Russo, Remo de Castro
Teixeira, Mauro Martins
dc.subject.other.pt_BR.fl_str_mv Células T CD8 +
Gravidade da doença
Células assassinas naturais
Neutrófilos
p38
Polimorfismo de nucleotídeo único
Type-I IFN
topic Células T CD8 +
Gravidade da doença
Células assassinas naturais
Neutrófilos
p38
Polimorfismo de nucleotídeo único
Type-I IFN
CD8+ T cells
Disease Severity
Natural killer cells
Neutrophils
p38
Single-nucleotide polymorphism
Type-I IFN
dc.subject.en.pt_BR.fl_str_mv CD8+ T cells
Disease Severity
Natural killer cells
Neutrophils
p38
Single-nucleotide polymorphism
Type-I IFN
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-08-24T16:44:27Z
dc.date.available.fl_str_mv 2018-08-24T16:44:27Z
dc.date.issued.fl_str_mv 2018
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv GARCIA, Cristiana Couto et al. Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients. Frontiers in Immunology, v. 9, p. 1-18, 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/28360
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2018.00975
identifier_str_mv GARCIA, Cristiana Couto et al. Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients. Frontiers in Immunology, v. 9, p. 1-18, 2018.
1664-3224
10.3389/fimmu.2018.00975
url https://www.arca.fiocruz.br/handle/icict/28360
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media AS
publisher.none.fl_str_mv Frontiers Media AS
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/28360/3/Phosphatidyl%20Inositol%203%20Kinase-Gamma%20Balances.pdf.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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