HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes

Recent evidence on HDAC6 function underlines its role as a key protein in the innate immune response to viral infection. However, whether HDAC6 regulates innate immunity during bacterial infection remains unexplored. To assess the role of HDAC6 in the regulation of defence mechanisms against intrace...

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Autores: Moreno-Gonzalo, Olga, Ramirez-Huesca, Marta, Blas-Rus, Noelia, Cibrián, Danay, Saiz, Maria Laura, Jorge, Inmaculada, Camafeita, Emilio, Vazquez, Jesus, Sanchez-Madrid, Francisco
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7244
Acceso en línea:http://hdl.handle.net/20.500.12105/7244
Access Level:acceso abierto
Palabra clave:Animals
Autophagy
Dendritic Cells
Female
Histone Deacetylase 6
Host-Pathogen Interactions
Humans
Interleukin-6
Listeria monocytogenes
Listeriosis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Signal Transduction
Toll-Like Receptors
Immunity, Innate
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/7244
network_acronym_str ES
network_name_str España
repository_id_str
spelling HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenesMoreno-Gonzalo, OlgaRamirez-Huesca, MartaBlas-Rus, NoeliaCibrián, DanaySaiz, Maria LauraJorge, InmaculadaCamafeita, EmilioVazquez, JesusSanchez-Madrid, FranciscoAnimalsAutophagyDendritic CellsFemaleHistone Deacetylase 6Host-Pathogen InteractionsHumansInterleukin-6Listeria monocytogenesListeriosisMaleMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Signal TransductionToll-Like ReceptorsImmunity, InnateRecent evidence on HDAC6 function underlines its role as a key protein in the innate immune response to viral infection. However, whether HDAC6 regulates innate immunity during bacterial infection remains unexplored. To assess the role of HDAC6 in the regulation of defence mechanisms against intracellular bacteria, we used the Listeria monocytogenes (Lm) infection model. Our data show that Hdac6-/- bone marrow-derived dendritic cells (BMDCs) have a higher bacterial load than Hdac6+/+ cells, correlating with weaker induction of IFN-related genes, pro-inflammatory cytokines and nitrite production after bacterial infection. Hdac6-/- BMDCs have a weakened phosphorylation of MAPK signalling in response to Lm infection, suggesting altered Toll-like receptor signalling (TLR). Compared with Hdac6+/+ counterparts, Hdac6-/- GM-CSF-derived and FLT3L-derived dendritic cells show weaker pro-inflammatory cytokine secretion in response to various TLR agonists. Moreover, HDAC6 associates with the TLR-adaptor molecule Myeloid differentiation primary response gene 88 (MyD88), and the absence of HDAC6 seems to diminish the NF-κB induction after TLR stimuli. Hdac6-/- mice display low serum levels of inflammatory cytokine IL-6 and correspondingly an increased survival to a systemic infection with Lm. The impaired bacterial clearance in the absence of HDAC6 appears to be caused by a defect in autophagy. Hence, Hdac6-/- BMDCs accumulate higher levels of the autophagy marker p62 and show defective phagosome-lysosome fusion. These data underline the important function of HDAC6 in dendritic cells not only in bacterial autophagy, but also in the proper activation of TLR signalling. These results thus demonstrate an important regulatory role for HDAC6 in the innate immune response to intracellular bacterial infection.Ministerio de Economía y Competitividad (España)Comunidad de Madrid (España)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Ministerio de Educación y Ciencia (España)Centro de Investigación Biomedica en Red - CIBERUnión Europea. Comisión EuropeaUnión Europea. Comisión Europea. European Research Council (ERC)Fundación ProCNIC20192019-02-2720172017-01-0120172017-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/7244reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 294340ES SEV-2015-0505 Not availableSAF2014-55579-R Not available Not availablePIE13 00041 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/72442026-06-12T12:43:37Z
dc.title.none.fl_str_mv HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
title HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
spellingShingle HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
Moreno-Gonzalo, Olga
Animals
Autophagy
Dendritic Cells
Female
Histone Deacetylase 6
Host-Pathogen Interactions
Humans
Interleukin-6
Listeria monocytogenes
Listeriosis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Signal Transduction
Toll-Like Receptors
Immunity, Innate
title_short HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
title_full HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
title_fullStr HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
title_full_unstemmed HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
title_sort HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
dc.creator.none.fl_str_mv Moreno-Gonzalo, Olga
Ramirez-Huesca, Marta
Blas-Rus, Noelia
Cibrián, Danay
Saiz, Maria Laura
Jorge, Inmaculada
Camafeita, Emilio
Vazquez, Jesus
Sanchez-Madrid, Francisco
author Moreno-Gonzalo, Olga
author_facet Moreno-Gonzalo, Olga
Ramirez-Huesca, Marta
Blas-Rus, Noelia
Cibrián, Danay
Saiz, Maria Laura
Jorge, Inmaculada
Camafeita, Emilio
Vazquez, Jesus
Sanchez-Madrid, Francisco
author_role author
author2 Ramirez-Huesca, Marta
Blas-Rus, Noelia
Cibrián, Danay
Saiz, Maria Laura
Jorge, Inmaculada
Camafeita, Emilio
Vazquez, Jesus
Sanchez-Madrid, Francisco
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Comunidad de Madrid (España)
Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Ministerio de Educación y Ciencia (España)
Centro de Investigación Biomedica en Red - CIBER
Unión Europea. Comisión Europea
Unión Europea. Comisión Europea. European Research Council (ERC)
Fundación ProCNIC
dc.subject.none.fl_str_mv Animals
Autophagy
Dendritic Cells
Female
Histone Deacetylase 6
Host-Pathogen Interactions
Humans
Interleukin-6
Listeria monocytogenes
Listeriosis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Signal Transduction
Toll-Like Receptors
Immunity, Innate
topic Animals
Autophagy
Dendritic Cells
Female
Histone Deacetylase 6
Host-Pathogen Interactions
Humans
Interleukin-6
Listeria monocytogenes
Listeriosis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
Signal Transduction
Toll-Like Receptors
Immunity, Innate
description Recent evidence on HDAC6 function underlines its role as a key protein in the innate immune response to viral infection. However, whether HDAC6 regulates innate immunity during bacterial infection remains unexplored. To assess the role of HDAC6 in the regulation of defence mechanisms against intracellular bacteria, we used the Listeria monocytogenes (Lm) infection model. Our data show that Hdac6-/- bone marrow-derived dendritic cells (BMDCs) have a higher bacterial load than Hdac6+/+ cells, correlating with weaker induction of IFN-related genes, pro-inflammatory cytokines and nitrite production after bacterial infection. Hdac6-/- BMDCs have a weakened phosphorylation of MAPK signalling in response to Lm infection, suggesting altered Toll-like receptor signalling (TLR). Compared with Hdac6+/+ counterparts, Hdac6-/- GM-CSF-derived and FLT3L-derived dendritic cells show weaker pro-inflammatory cytokine secretion in response to various TLR agonists. Moreover, HDAC6 associates with the TLR-adaptor molecule Myeloid differentiation primary response gene 88 (MyD88), and the absence of HDAC6 seems to diminish the NF-κB induction after TLR stimuli. Hdac6-/- mice display low serum levels of inflammatory cytokine IL-6 and correspondingly an increased survival to a systemic infection with Lm. The impaired bacterial clearance in the absence of HDAC6 appears to be caused by a defect in autophagy. Hence, Hdac6-/- BMDCs accumulate higher levels of the autophagy marker p62 and show defective phagosome-lysosome fusion. These data underline the important function of HDAC6 in dendritic cells not only in bacterial autophagy, but also in the proper activation of TLR signalling. These results thus demonstrate an important regulatory role for HDAC6 in the innate immune response to intracellular bacterial infection.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01
2017
2017-01-01
2019
2019-02-27
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/7244
url http://hdl.handle.net/20.500.12105/7244
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 294340
ES SEV-2015-0505 Not available
SAF2014-55579-R Not available Not available
PIE13 00041 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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