Evidence of collective influence in innate sensing using fluidic force microscopy

Elizabeth J. Mulder, Brittany Moser, Jennifer Delgado, Rachel C. Steinhardt, Aaron P. Esser-Kahn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The innate immune system initiates early response to infection by sensing molecular patterns of infection through pattern-recognition receptors (PRRs). Previous work on PRR stimulation of macrophages revealed significant heterogeneity in single cell responses, suggesting the importance of individual macrophage stimulation. Current methods either isolate individual macrophages or stimulate a whole culture and measure individual readouts. We probed single cell NF-κB responses to localized stimuli within a naïve culture with Fluidic Force Microscopy (FluidFM). Individual cells stimulated in naïve culture were more sensitive compared to individual cells in uniformly stimulated cultures. In cluster stimulation, NF-κB activation decreased with increased cell density or decreased stimulation time. Our results support the growing body of evidence for cell-to-cell communication in macrophage activation, and limit potential mechanisms. Such a mechanism might be manipulated to tune macrophage sensitivity, and the density-dependent modulation of sensitivity to PRR signals could have relevance to biological situations where macrophage density increases.

Original languageEnglish (US)
Article number1340384
JournalFrontiers in Immunology
Volume15
DOIs
StatePublished - 2024
Externally publishedYes

Keywords

  • FluidFM
  • fluidic force microscopy
  • innate immunity
  • macrophage
  • NF-κB
  • quorum licensing
  • RAW 264.7
  • resiquimod

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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