Immune quorum sensing dictates IFN-I response dynamics in human plasmacytoid dendritic cells

Laura C. Van Eyndhoven (Corresponding author), Cherise C. Vreezen, Bart M. Tiemeijer, Jurjen Tel

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Samenvatting

Type I interferons (IFN-Is) are key in fighting viral infections, but also serve major roles beyond antiviral immunity. Crucial is the tight regulation of IFN-I responses, while excessive levels are harmful to the cells. In essence, immune responses are generated by single cells making their own decisions, which are based on the signals they perceive. Additionally, immune cells must anticipate the future state of their environment, thereby weighing the costs and benefits of each possible outcome, in the presence of other potentially competitive decision makers (i.e., IFN-I producing cells). A rather new cellular communication mechanism called quorum sensing describes the effect of cell density on cellular secretory behaviors, which fits well with matching the right amount of IFN-Is produced to fight an infection. More competitive decision makers must contribute relatively less and vice versa. Intrigued by this concept, we assessed the effects of immune quorum sensing in pDCs, specialized immune cells known for their ability to mass produce IFN-Is. Using conventional microwell assays and droplet-based microfluidics assays, we were able the characterize the effect of quorum sensing in human primary immune cells in vitro. These insights open new avenues to manipulate IFN-I response dynamics in pathological conditions affected by aberrant IFN-I signaling.

Originele taal-2Engels
Artikelnummer2350955
Aantal pagina's12
TijdschriftEuropean Journal of Immunology
Volume54
Nummer van het tijdschrift7
Vroegere onlinedatum8 apr. 2024
DOI's
StatusGepubliceerd - jul. 2024

Financiering

This work was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 802791). Finally, the authors would like to acknowledge the generous support by the Eindhoven University of Technology.

FinanciersFinanciernummer
European Research Council
Technische Universiteit Eindhoven
Horizon 2020802791

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