Legionella pneumophila-Derived Outer Membrane Vesicles Promote Bacterial Replication in Macrophages
Publication Date
April 22, 2016
Journal
PLOS Pathogens
Authors
Anna Lena Jung, Cornelia Stoiber, Christina E. Herkt, Christine Schulz, et al
Volume
12
Issue
4
Pages
e1005592
DOI
https://dx.plos.org/10.1371/journal.ppat.1005592
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005592
Web of Science
000378156900062
Scopus
84964896822
Mendeley
http://www.mendeley.com/research/legionella-pneumophiladerived-outer-membrane-vesicles-promote-bacterial-replication-macrophages
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Mendeley | Further Information

{"title"=>"Legionella pneumophila-Derived Outer Membrane Vesicles Promote Bacterial Replication in Macrophages", "type"=>"journal", "authors"=>[{"first_name"=>"Anna Lena", "last_name"=>"Jung", "scopus_author_id"=>"57189039907"}, {"first_name"=>"Cornelia", "last_name"=>"Stoiber", "scopus_author_id"=>"57189046590"}, {"first_name"=>"Christina E.", "last_name"=>"Herkt", "scopus_author_id"=>"56998710700"}, {"first_name"=>"Christine", "last_name"=>"Schulz", "scopus_author_id"=>"57189040842"}, {"first_name"=>"Wilhelm", "last_name"=>"Bertrams", "scopus_author_id"=>"55581088100"}, {"first_name"=>"Bernd", "last_name"=>"Schmeck", "scopus_author_id"=>"6603354847"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"84964896822", "pmid"=>"27105429", "pui"=>"610216880", "issn"=>"15537374", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "scopus"=>"2-s2.0-84964896822", "doi"=>"10.1371/journal.ppat.1005592"}, "id"=>"54188e1d-1940-3dd4-a9e3-66b65e2b5711", "abstract"=>"The formation and release of outer membrane vesicles (OMVs) is a phenomenon of Gram-negative bacteria. This includes Legionella pneumophila (L. pneumophila), a causative agent of severe pneumonia. Upon its transmission into the lung, L. pneumophila primarily infects and replicates within macrophages. Here, we analyzed the influence of L. pneumophila OMVs on macrophages. To this end, differentiated THP-1 cells were incubated with increasing doses of Legionella OMVs, leading to a TLR2-dependent classical activation of macrophages with the release of pro-inflammatory cytokines. Inhibition of TLR2 and NF-kappaB signaling reduced the induction of pro-inflammatory cytokines. Furthermore, treatment of THP-1 cells with OMVs prior to infection reduced replication of L. pneumophila in THP-1 cells. Blocking of TLR2 activation or heat denaturation of OMVs restored bacterial replication in the first 24 h of infection. With prolonged infection-time, OMV pre-treated macrophages became more permissive for bacterial replication than untreated cells and showed increased numbers of Legionella-containing vacuoles and reduced pro-inflammatory cytokine induction. Additionally, miRNA-146a was found to be transcriptionally induced by OMVs and to facilitate bacterial replication. Accordingly, IRAK-1, one of miRNA-146a's targets, showed prolonged activation-dependent degradation, which rendered THP-1 cells more permissive for Legionella replication. In conclusion, L. pneumophila OMVs are initially potent pro-inflammatory stimulators of macrophages, acting via TLR2, IRAK-1, and NF-kappaB, while at later time points, OMVs facilitate L. pneumophila replication by miR-146a-dependent IRAK-1 suppression. OMVs might thereby promote spreading of L. pneumophila in the host.", "link"=>"http://www.mendeley.com/research/legionella-pneumophiladerived-outer-membrane-vesicles-promote-bacterial-replication-macrophages", "reader_count"=>29, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>9, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>2, "Chemical Engineering"=>1, "Immunology and Microbiology"=>4, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>2}

Scopus | Further Information

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