{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:29:08Z","timestamp":1790947748124,"version":"4.1.0"},"reference-count":29,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:p>Influenza A Virus (IAV), &lt;i&gt;Staphylococcus aureus&lt;\/i&gt; (staphylococci), and &lt;i&gt;Streptococcus pneumoniae&lt;\/i&gt; (pneumococci) are leading viral and bacterial causes of pneumonia. Dendritic cells (DCs) are present in the lower respiratory tract. They are characterized by low expression of co-stimulatory molecules, including CD80 and CD86 and high capacity of antigen uptake. Subsequently, DCs upregulate co-stimulatory signals and cytokine secretion to effectively induce T-cell priming. Here, we investigated these processes in response to bacterial and viral single as well as coinfections using human monocyte-derived (mo)DCs. Irrespective of single or coinfections, moDCs matured in response to IAV and\/or staphylococcal infections, secreted a wide range of cytokines, and activated CD4&lt;sup&gt;+&lt;\/sup&gt;, CD8&lt;sup&gt;+&lt;\/sup&gt; as well as double-negative T cells. In contrast, pneumococcal single and coinfections impaired moDC maturation, which was characterized by low expression of CD80 and CD86, downregulated expression of CD40, and a mild cytokine release resulting in abrogated CD4&lt;sup&gt;+&lt;\/sup&gt; T-cell activation. These actions were attributed to the cholesterol-dependent cytotoxin pneumolysin (Ply). Infections with a &lt;i&gt;ply&lt;\/i&gt;-deficient mutant resulted in restored moDC maturation and exclusive CD4&lt;sup&gt;+&lt;\/sup&gt; T-cell activation. These findings show that Ply has important immunomodulatory functions, supporting further investigations in specific modalities of Ply-DC interplay. <\/jats:p>","DOI":"10.1159\/000522339","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T22:00:49Z","timestamp":1646431249000},"page":"569-580","source":"Crossref","is-referenced-by-count":11,"title":["&lt;b&gt;&lt;i&gt;Streptococcus pneumoniae&lt;\/i&gt;&lt;\/b&gt; Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4&lt;sup&gt;+&lt;\/sup&gt; T Cells via Pneumolysin"],"prefix":"10.1159","volume":"14","author":[{"given":"Antje D.","family":"Paulikat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea A.","family":"T\u00f6lken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana H.","family":"Jachmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Burchhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-6681","authenticated-orcid":false,"given":"Sven","family":"Hammerschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Siemens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.10.5132"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.151.5.1196"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/32588"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/nri723"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.2.389"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.09.040191.001415"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/nri727"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/s1471-4906(02)02319-0"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/s0966-842x(01)02254-5"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200101043440102"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00058-05"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3231"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02611.x"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/srep38013"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900025"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1159\/000517855"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.180"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01851-14"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02603"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60733-4"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.001"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/521957"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a030338"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00168-16"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202010"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36731"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1177\/1753425920917731"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01643"}],"container-title":["Journal of Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/522339","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/522339","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:49:57Z","timestamp":1745423397000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000522339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,9,2]]}},"URL":"https:\/\/doi.org\/10.1159\/000522339","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.19307654","asserted-by":"subject"}]},"ISSN":["1662-811X","1662-8128"],"issn-type":[{"value":"1662-811X","type":"print"},{"value":"1662-8128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}