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Related Experiment Videos

Cellular Decision Making by Non-Integrative Processing of TLR Inputs.

Ryan A Kellogg1, Chengzhe Tian2, Martin Etzrodt3

  • 1Department of Biosystems Science and Engineering, ETH Zürich 4058, Switzerland; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.

Cell Reports
|April 6, 2017
PubMed
Summary

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Cells exhibit "non-integrative" processing of simultaneous signals, responding distinctly to Toll-like receptor 2 (TLR2) or TLR4 activation rather than integrating inputs. This finding reveals complex cellular decision-making during infection responses.

Area of Science:

  • Immunology
  • Cellular Biology
  • Systems Biology

Background:

  • Cells integrate environmental signals for survival and function.
  • Toll-like receptors (TLRs) initiate inflammatory responses upon pathogen detection.
  • Understanding simultaneous TLR signaling is crucial for deciphering cellular responses to infection.

Purpose of the Study:

  • To investigate how cells process simultaneous signals from Toll-like receptor 4 (TLR4) and Toll-like receptor 2 (TLR2).
  • To characterize the dynamic nuclear factor κB (NF-κB) pathway activation under co-stimulation.
  • To elucidate the mechanisms underlying cellular signal processing.

Main Methods:

  • Microfluidic experiments to co-stimulate cells with TLR4 and TLR2 ligands.
  • Quantitative analysis of nuclear factor κB (NF-κB) dynamics in single cells.
Keywords:
digitaldynamicsimmunityinformation processinglive-cell imagingmicrofluidicssignalingsingle cellsynergytoll-like receptors

Related Experiment Videos

  • Iterative computational modeling to explain observed signaling patterns.

    • Main Results:

    • Independent TLR2 and TLR4 stimulation induced distinct NF-κB dynamic profiles.
    • Under co-stimulation, single cells displayed ligand-specific responses (TLR2 or TLR4), not integrated responses.
    • This phenomenon, termed "non-integrative" processing, was explained by switch-like NF-κB activation, receptor-specific timescales, cell variability, and negative feedback.

    Conclusions:

    • Cells employ "non-integrative" processing for simultaneous TLR signaling.
    • This cellular decision involves complex interplay of signaling dynamics, variability, and feedback mechanisms.
    • Findings provide new insights into immune signal integration and cellular decision-making during infection.