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

被引:7
作者
Paulikat, Antje D. [1 ]
Toelken, Lea A. [1 ]
Jachmann, Lana H. [1 ]
Burchhardt, Gerhard [1 ]
Hammerschmidt, Sven [1 ]
Siemens, Nikolai [1 ]
机构
[1] Univ Greifswald, Dept Mol Genet & Infect Biol, Greifswald, Germany
关键词
Dendritic cells; Streptococcus pneumoniae; Staphylococcus aureus; Influenza A virus; Pneumolysin; IMMUNE-RESPONSES; INFLUENZA-VIRUS; NASAL CARRIAGE; RECEPTOR; INNATE; CD40;
D O I
10.1159/000522339
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:12
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[41]   Bronchial Epithelial Cells Accumulate Citrate Intracellularly in Response to Pneumococcal Hydrogen Peroxide [J].
Surabhi, Surabhi ;
Jachmann, Lana H. ;
Lalk, Michael ;
Hammerschmidt, Sven ;
Methling, Karen ;
Siemens, Nikolai .
ACS INFECTIOUS DISEASES, 2021, 7 (11) :2971-2978
[42]   Hydrogen Peroxide Is Crucial for NLRP3 Inflammasome-Mediated IL-1β Production and Cell Death in Pneumococcal Infections of Bronchial Epithelial Cells [J].
Surabhi, Surabhi ;
Jachmann, Lana H. ;
Shumba, Patience ;
Burchhardt, Gerhard ;
Hammerschmidt, Sven ;
Siemens, Nikolai .
JOURNAL OF INNATE IMMUNITY, 2022, 14 (03) :192-206
[43]   The pathology of influenza virus infections [J].
Taubenberger, Jeffery K. ;
Morens, David M. .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2008, 3 :499-522
[44]   Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules [J].
Valladeau, J ;
Ravel, O ;
Dezutter-Dambuyant, C ;
Moore, K ;
Kleijmeer, M ;
Liu, Y ;
Duvert-Frances, V ;
Vincent, C ;
Schmitt, D ;
Davoust, J ;
Caux, C ;
Lebecque, S ;
Saeland, S .
IMMUNITY, 2000, 12 (01) :71-81
[45]  
Vallés J, 2016, MED INTENSIVA, V40, P238, DOI [10.1016/j.medine.2016.04.004, 10.1016/j.medin.2015.07.005]
[46]   Co-evolutionary aspects of human colonisation and infection by Staphylococcus aureus [J].
van Belkum, Alex ;
Melles, Damian C. ;
Nouwen, Jan ;
van Leeuwen, Willem B. ;
van Wamel, Willem ;
Vos, Margreet C. ;
Wertheim, Heiman F. L. ;
Verbrugh, Henri A. .
INFECTION GENETICS AND EVOLUTION, 2009, 9 (01) :32-47
[47]   Nasal carriage as a source of Staphylococcus aureus bacteremia. [J].
von Eiff, C ;
Becker, K ;
Machka, K ;
Stammer, H ;
Peters, G .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (01) :11-16
[48]   Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice [J].
Zhang, Zhe ;
Clarke, Thomas B. ;
Weiser, Jeffrey N. .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (07) :1899-1909
[49]   Plasticity of CD4+ T Cell Lineage Differentiation [J].
Zhou, Liang ;
Chong, Mark M. W. ;
Littman, Dan R. .
IMMUNITY, 2009, 30 (05) :646-655
[50]   T Helper Cell Differentiation, Heterogeneity, and Plasticity [J].
Zhu, Jinfang .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2018, 10 (10)