HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes
Publication Date
December 27, 2017
Authors
Olga Moreno Gonzalo, Marta Ramírez Huesca, Noelia Blas Rus, Danay Cibrián, et al
Volume
13
Issue
12
Pages
e1006799
DOI
https://dx.plos.org/10.1371/journal.ppat.1006799
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006799
Scopus
85039902933
Mendeley
http://www.mendeley.com/research/hdac6-controls-innate-immune-autophagy-responses-tlrmediated-signalling-intracellular-bacteria-liste
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Mendeley | Further Information

{"title"=>"HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes", "type"=>"journal", "authors"=>[{"first_name"=>"Olga", "last_name"=>"Moreno-Gonzalo", "scopus_author_id"=>"55256231800"}, {"first_name"=>"Marta", "last_name"=>"Ramírez-Huesca", "scopus_author_id"=>"6507485131"}, {"first_name"=>"Noelia", "last_name"=>"Blas-Rus", "scopus_author_id"=>"57189599640"}, {"first_name"=>"Danay", "last_name"=>"Cibrián", "scopus_author_id"=>"13605765900"}, {"first_name"=>"María Laura", "last_name"=>"Saíz", "scopus_author_id"=>"57093483400"}, {"first_name"=>"Inmaculada", "last_name"=>"Jorge", "scopus_author_id"=>"9232530800"}, {"first_name"=>"Emilio", "last_name"=>"Camafeita", "scopus_author_id"=>"6602578497"}, {"first_name"=>"Jesús", "last_name"=>"Vázquez", "scopus_author_id"=>"7401760670"}, {"first_name"=>"Francisco", "last_name"=>"Sánchez-Madrid", "scopus_author_id"=>"7102563014"}], "year"=>2017, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"85039902933", "pui"=>"620067293", "issn"=>"15537374", "isbn"=>"1111111111", "scopus"=>"2-s2.0-85039902933", "doi"=>"10.1371/journal.ppat.1006799"}, "id"=>"14f31805-e2c8-340a-9c33-1c1044c6dfd9", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/hdac6-controls-innate-immune-autophagy-responses-tlrmediated-signalling-intracellular-bacteria-liste", "reader_count"=>7, "reader_count_by_academic_status"=>{"Librarian"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>3, "Other"=>1}, "reader_count_by_user_role"=>{"Librarian"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>3, "Other"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>3, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "group_count"=>0}

Scopus | Further Information

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