Bronchial Epithelial Cells Accumulate Citrate Intracellularly in Response to Pneumococcal Hydrogen Peroxide

Surabhi, Surabhi; Jachmann, Lana H; Lalk, Michael; Hammerschmidt, Sven; Methling, Karen; Siemens, Nikolai

doi:10.1021/acsinfecdis.1c00372

Cited by 5 publications

(6 citation statements)

References 30 publications

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“…All infections were performed in RPMI1640 complete media. 1 × 10 5 monocyte-derived DCs (moDCs) were infected with H1N1 at a multiplicity of infection 0.1 for 24 h [ 30 ]. To warrant comparable initial bacterial infection rates, moDCs were infected at multiplicity of infection 10 for 3 h with pneumococci and 1 h with staphylococci.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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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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Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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“…Infections of monocytes and macrophages were performed in RPMI1640 media supplemented with 10% FCS. Furthermore, 1 × 10 5 monocytes or 2 × 10 5 monocyte-derived macrophages were infected with H1N1 at an MOI of 0.1 for 24 hours 41 . The MOI was chosen based on previous results, showing equal viral loads for a range of tested MOIs 18,41 .…”

Section: Methodsmentioning

confidence: 99%

“…41 The MOI was chosen based on previous results, showing equal viral loads for a range of tested MOIs. 18,41 Macrophages and monocytes were infected with SA113 at MOIs of 10 and 1, respectively. After one hour, the medium was removed, and extracellular bacteria were killed by addition of RPMI1640 containing 400μg/mL gentamicin or 2-μg/mL lysostaphin (both Sigma-Aldrich).…”

Section: Eukaryotic Cells Culture Conditions and Infectionsmentioning

confidence: 99%

“…Furthermore, 1 Â 10 5 monocytes or 2 Â 10 5 monocyte-derived macrophages were infected with H1N1 at an MOI of 0.1 for 24 hours. 41 The MOI was chosen based on previous results, showing equal viral loads for a range of tested MOIs. 18,41 Macrophages and monocytes were infected with SA113 at MOIs of 10 and 1, respectively.…”

Section: Eukaryotic Cells Culture Conditions and Infectionsmentioning

confidence: 99%

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Cytokine Profiling in Influenza A Virus and Staphylococcal (Co-)Infections

Tölken¹,

Paulikat²,

Cuypers³

et al. 2022

Infect Microb Dis

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Influenza A virus and Staphylococcus aureus are common causative agents of pneumonia. Co-infections with these two pathogens frequently occur and are characterized, among others, by higher morbidity and mortality due to hyper-inflammation of the lungs. Here, we aimed to profile systemic and local cytokine composition at early acute stages of pneumonia in a murine model. All mice recovered from single influenza A virus and/or staphylococcal infections. In contrast, co-infections led to a severe clinical outcome. While distinct cytokine patterns were detected in lungs of single-pathogen-infected animals, co-infections combined both virus- and bacteria-driven responses. However, analyses of infected human primary monocytic cells as well as bronchial epithelial cells did not reflect murine profiles. Based on infectious dose, mainly bacteria-driven responses were noted. The impact of single cells to cytokine composition of the lungs and translation of murine studies to humans remains uncertain and warrants further studies.

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“…Stable isotopic labeled internal standard compounds were used as described before. [32] Absolute concentrations of metabolites were determined with a calibration curve ranging from 0.05 to 100 nmol/ sample for each metabolite. All metabolite concentrations were normalized to the wet weight of colonies.…”

Section: Analysis Of Biofilm Metabolites and Metabolites Of Lb Medium...mentioning

confidence: 99%

A Targeted Approach for the Metabolome Analysis of E. coli Biofilms

Rockstroh,

Gerschler,

Schultze

et al. 2024

Helvetica Chimica Acta

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Biofilms of pathogenic bacteria are responsible for persistent infections in humans, therefore investigations of biofilm formation and treatment strategies are required. The gram‐negative enterobacterium Escherichia (E.) coli is the most common pathogen causing chronic or recurring urinary tract infections. Metabolomics approaches targeted the bacterium to investigate specific metabolic patterns of biofilms and regulatory influences on biofilm formation. In this study, we aimed to investigate the metabolome of biofilms formed by the multidrug‐resistant extended‐spectrum beta‐lactamase‐producing (ESBL) E. coliPBIO729. For this purpose, a protocol for fast sampling of the macrocolony biofilms and efficient extraction of metabolites was optimized. Validation of an LC‐MS/MS method confirmed its usability for the analysis of nucleotides and other phosphorylated metabolites. A GC‐MS approach was used to monitor nutrient uptake from the medium in addition to the analysis of amino acid content and metabolites of glycolysis and TCA cycle in E. coli biofilms.

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Bronchial Epithelial Cells Accumulate Citrate Intracellularly in Response to Pneumococcal Hydrogen Peroxide

Cited by 5 publications

References 30 publications

<b><i>Streptococcus pneumoniae</i></b> Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4<sup>+</sup> T Cells via Pneumolysin

<b><i>Streptococcus pneumoniae</i></b> Impairs Maturation of Human Dendritic Cells and Consequent Activation of CD4<sup>+</sup> T Cells via Pneumolysin

Cytokine Profiling in Influenza A Virus and Staphylococcal (Co-)Infections

A Targeted Approach for the Metabolome Analysis of E. coli Biofilms

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