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Updated: Aug 5, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

Non-canonical TLR signaling restricts cytosolic LPS detection

Shriram Ramani, Sara Cahill, Matthew Finnegan

    Biorxiv : the Preprint Server for Biology
    |July 29, 2026
    PubMed

    Insights

    MARCO acts as a decoy sensor for lipopolysaccharide (LPS), controlling the non-canonical inflammasome. Its regulation by a unique TLR pathway reveals a switch for immune homeostasis and inflammation resolution.

    Area of Science:

    • Immunology
    • Cellular Biology
    • Molecular Medicine

    Background:

    • Intracellular lipopolysaccharide (LPS) sensing is vital for innate immunity.
    • Mechanisms controlling LPS sensing for immune homeostasis remain unclear.

    Purpose of the Study:

    • To identify novel regulators of intracellular LPS sensing.
    • To elucidate the role of MARCO in restraining inflammasome activation.

    Main Methods:

    • Investigated MARCO's function as an LPS sensor.
    • Characterized a non-canonical Toll-like receptor (TLR) signaling pathway regulating MARCO.
    • Utilized mouse models to assess the impact of MARCO deficiency on immune responses and septic shock.

    Main Results:

    • MARCO functions as a decoy LPS sensor, inhibiting caspase 11 and the non-canonical inflammasome.
    • MARCO expression is controlled by itaconate, p62, and NRF2 via a non-canonical TLR pathway.
    • IFN impairs this pathway, reducing MARCO and enhancing inflammasome activation.
    • MARCO deficiency exacerbates inflammasome activation and septic shock.

    Conclusions:

    • MARCO is a novel LPS sensor critical for restraining non-canonical inflammasome activation.
    • A non-canonical TLR pathway regulates MARCO, acting as a homeostatic switch for immune responses.
    • Understanding this pathway offers insights into managing inflammation and sepsis.

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