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Bitte verwenden Sie diesen Link, wenn Sie dieses Dokument zitieren oder verlinken wollen: https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-87914

Streptococcus pneumoniae Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4+ T Cells via Pneumolysin

  • Influenza A Virus (IAV), Staphylococcus aureus (staphylococci), and Streptococcus pneumoniae (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+, CD8+ 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+ T-cell activation. These actions were attributed to the cholesterol-dependent cytotoxin pneumolysin (Ply). Infections with a ply-deficient mutant resulted in restored moDC maturation and exclusive CD4+ T-cell activation. These findings show that Ply has important immunomodulatory functions, supporting further investigations in specific modalities of Ply-DC interplay.

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Metadaten
Author: Antje D. Paulikat, Lea A. Tölken, Lana H. Jachmann, Gerhard Burchhardt, Sven Hammerschmidt, Nikolai Siemens
URN:urn:nbn:de:gbv:9-opus-87914
DOI:https://doi.org/10.1159/000522339
ISSN:1662-8128
Parent Title (English):Journal of Innate Immunity
Publisher:Karger
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2022/03/04
Date of first Publication:2022/09/01
Release Date:2024/01/15
Tag:Dendritic cells; Influenza A virus; Pneumolysin; Staphylococcus aureus; Streptococcus pneumoniae
Volume:14
Issue:5
First Page:569
Last Page:580
Faculties:Mathematisch-Naturwissenschaftliche Fakultät / Interfakultäres Institut für Genetik und Funktionelle Genomforschung (MNF)
Collections:DFG-geförderte Artikel
Licence (German):License LogoCreative Commons - Namensnennung