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Regulation of TLR3 Activation by S100A9
Su-Yu Tsai1, Jesus A Segovia2, Te-Hung Chang2
1Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164; Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229;
Journal of Immunology (Baltimore, Md. : 1950)
|September 20, 2015
Summary
Intracellular S100A9 protein is essential for TLR3 trafficking and innate immune response activation. S100A9 facilitates early endosome maturation, enabling TLR3 to recognize viral dsRNA and trigger cytokine production.
Area of Science:
- Immunology
- Cell Biology
Background:
- Endosomal Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) to initiate innate immune responses.
- TLR3 trafficking to the endolysosomal compartment is crucial for pathogen-associated molecular pattern recognition and subsequent signaling.
- Mechanisms governing TLR3 trafficking remain incompletely understood.
Purpose of the Study:
- To identify cellular factors regulating TLR3 trafficking.
- To elucidate the role of S100A9 protein in TLR3-mediated innate immunity.
Main Methods:
- Utilized S100A9-knockout (KO) mice and primary macrophages.
- Infection with RNA virus and treatment with polyinosinic-polycytidylic acid (polyIC).
- Confocal microscopy for colocalization studies and cytokine production assays.
Main Results:
- S100A9 is required for the maturation of early endosomes containing TLR3 into late endosomes.
- S100A9-deficient macrophages and mice showed significantly reduced cytokine production upon dsRNA stimulation.
- S100A9 directly interacts with TLR3, facilitating its proper localization for agonist recognition.
Conclusions:
- Intracellular S100A9 protein is a critical regulator of TLR3 trafficking and function.
- S100A9 facilitates the maturation of endosomes, enabling TLR3 to engage with viral dsRNA and activate innate immunity.
- S100A9 represents a novel target for modulating TLR3-dependent immune responses.
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