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

Autor: Paulikat AD; Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany., Tölken LA; Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany., Jachmann LH; Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany., Burchhardt G; Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany., Hammerschmidt S; Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany., Siemens N; Department of Molecular Genetics and Infection Biology, University of Greifswald, Greifswald, Germany.
Jazyk: angličtina
Zdroj: Journal of innate immunity [J Innate Immun] 2022; Vol. 14 (5), pp. 569-580. Date of Electronic Publication: 2022 Mar 04.
DOI: 10.1159/000522339
Abstrakt: 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.
(© 2022 The Author(s). Published by S. Karger AG, Basel.)
Databáze: MEDLINE
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