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, incl...

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Main Authors: Antje D. Paulikat (Author), Lea A. Tölken (Author), Lana H. Jachmann (Author), Gerhard Burchhardt (Author), Sven Hammerschmidt (Author), Nikolai Siemens (Author)
Format: Book
Published: Karger Publishers, 2022-03-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Antje D. Paulikat  |e author 
700 1 0 |a Lea A. Tölken  |e author 
700 1 0 |a Lana H. Jachmann  |e author 
700 1 0 |a Gerhard Burchhardt  |e author 
700 1 0 |a Sven Hammerschmidt  |e author 
700 1 0 |a Nikolai Siemens  |e author 
245 0 0 |a Streptococcus pneumoniae Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4+ T Cells via Pneumolysin 
260 |b Karger Publishers,   |c 2022-03-01T00:00:00Z. 
500 |a 1662-811X 
500 |a 1662-8128 
500 |a 10.1159/000522339 
520 |a 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. 
546 |a EN 
690 |a dendritic cells 
690 |a streptococcus pneumoniae 
690 |a staphylococcus aureus 
690 |a influenza a virus 
690 |a pneumolysin 
690 |a Medicine 
690 |a R 
690 |a Internal medicine 
690 |a RC31-1245 
655 7 |a article  |2 local 
786 0 |n Journal of Innate Immunity, Pp 1-12 (2022) 
787 0 |n https://www.karger.com/Article/FullText/522339 
787 0 |n https://doaj.org/toc/1662-811X 
787 0 |n https://doaj.org/toc/1662-8128 
856 4 1 |u https://doaj.org/article/4d5ed1b57b31447bb7af59bc7c4088c1  |z Connect to this object online.