Show simple item record

dc.contributor.authorMoreno-Gonzalo, Olga 
dc.contributor.authorRamirez-Huesca, Marta 
dc.contributor.authorBlas-Rus, Noelia 
dc.contributor.authorCibrián, Danay
dc.contributor.authorSaiz, Maria Laura 
dc.contributor.authorJorge, Inmaculada 
dc.contributor.authorCamafeita, Emilio 
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorSanchez-Madrid, Francisco
dc.identifier.citationPLoS Pathog. 2017; 13(12):e1006799es_ES
dc.description.abstractRecent 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.es_ES
dc.description.sponsorshipThe funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported by the following grants to FSM: SAF2014-55579-R from the Spanish Ministry of Economy and Competitiveness, INDISNET-S2011/ BMD-2332 from the Comunidad de Madrid, CIBER CARDIOVASCULAR and grant PIE13/00041 from the Instituto de Salud Carlos III (Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III with co-funding from the Fondo Europeo de Desarrollo Regional; FEDER), and ERC-2011-AdG 294340- GENTRIS and COST-Action BM1202 from the European Comission. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). OMG was supported by the fellowship FPU programme (Spanish Ministry of Education). MLS was supported by the fellowship FPI programme (Spanish Ministry of Economy).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAutophagy es_ES
dc.subject.meshDendritic Cells es_ES
dc.subject.meshFemale es_ES
dc.subject.meshHistone Deacetylase 6 es_ES
dc.subject.meshHost-Pathogen Interactions es_ES
dc.subject.meshHumans es_ES
dc.subject.meshInterleukin-6 es_ES
dc.subject.meshListeria monocytogenes es_ES
dc.subject.meshListeriosis es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshMyeloid Differentiation Factor 88 es_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshToll-Like Receptors es_ES
dc.subject.meshImmunity, Innate es_ES
dc.titleHDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogeneses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderMinisterio de Educación y Ciencia (España)es_ES
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBERes_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderEuropean Research Counciles_ES
dc.contributor.funderFundación ProCNICes_ES
dc.identifier.journalPLoS pathogenses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoriaes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovasculares_ES

Files in this item

Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Atribución 4.0 Internacional
This item is licensed under a: Atribución 4.0 Internacional