Impact of chemical mixtures from wastewater treatment plant effluents on human immune cell activation: An effect-based analysis

Maddalon, Ambra; Pierzchalski, Arkadiusz; Krause, Jannike Lea; Bauer, Mario; Finckh, Saskia; Brack, Werner; Zenclussen, Ana C.; Marinovich, Marina; Corsini, Emanuela; Krauss, Martin; Herberth, Gunda

doi:10.1016/j.scitotenv.2023.167495

Cited by 3 publications

(2 citation statements)

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“…The method described here can be used for the evaluation of MAIT cell responses upon stimulation with E.coli. We already used a similar method for the evaluation of chemical effects on these cells for bisphenols, PFAS and samples from wastewater treatment plants (WWTP) ( 13 , 14 , 40 ). The other assay we propose, the cytokine activation of MAIT cells via mixture of IL-12/15/18, serves as surrogate for antigen-independent MAIT cells activation which mimics innate/adaptive immune response leading to chronic activation ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…The chemical effects are expressed as fold change relative to the corresponding control. This allows the focus to be on the modulation of this stimulation by the chemical exposure, rather than the individual variability of the response to the stimulant ( 14 , 40 ). It is also a limitation that important immunomodulatory cytokines such as IL-10, IL-17 and TGF−β were not included in our tests because they are barely expressed after the short incubation times we used.…”

Section: Discussionmentioning

confidence: 99%

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A comprehensive battery of flow cytometric immunoassays for the in vitro testing of chemical effects in human blood cells

Pierzchalski,

Zenclussen,

Herberth

2024

Front. Immunol.

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BackgroundThere is a growing need for immunological assays to test toxic and modulatory effects of chemicals. The assays should be easy to use, reproducible and superior to cell line-based assays. We have therefore developed a comprehensive portfolio of assays based on primary human blood cells that are suitable for testing chemical effects.MethodsThe flow cytometry-based assays were designed to target a wide range of human peripheral blood mononuclear cells and whole blood, including T cells, NK cells, B cells, basophils and innate-like T cells such as γδT, MAIT and NKT cells. We have selected a set of activation markers for each immune cell, e.g: CD154 (T cells), CD137, CD107a (NK cells), CD63 (basophils), CD69, CD83 (B cells), CD69, IFN-γ (MAIT cells) and we selected cell specific stimuli: aCD3 antibodies (T cells); E. coli and cytokines IL-12/15/18 (MAIT cells); CpG ODN2006, R848 or aCD40 antibodies (B cells), fMLP or aFcϵR1 (basophils) or K562 cells (NK cells).ResultsBy selecting immune cell-specific markers and cell-specific stimuli, we were able to induce particular immune responses from the targeted immune cells. For example, the response to stimulation with anti-CD3 antibodies was in 36.8% of CD107a+CD8+ cells. Cytokine stimulation induced the production of IFN-γ in 30% of MAIT cells. After stimulation with E. coli, around 50% of MAIT cells produced TNF. About 40% of basophils responded to aFcƐR1 stimulation. Similar activation ranges were achieved in K562-stimulated NK cells.ConclusionOur test portfolio covers the most relevant immune cells present in human blood, providing a solid basis for in vitro toxicity and immunomodulatory testing of chemicals. By using human blood, the natural composition of cells found in the blood can be determined and the effects of chemicals can be detected at the cellular level.

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