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Hedgehog: linking uracil to innate defense.
1Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0349, USA.
Cell Host & Microbe
|February 13, 2015
Summary
Pathogen-secreted uracil triggers reactive oxygen species (ROS) production in the gut. This discovery explains how the gut epithelium balances pathogen defense and commensal tolerance via the Hedgehog pathway.
Area of Science:
- Gut immunity
- Microbial-epithelial interactions
- Cell signaling
Background:
- The gut epithelium must distinguish between harmful pathogens and beneficial commensals.
- Mechanisms underlying this selective defense are not fully understood.
Purpose of the Study:
- To investigate how pathogen molecules influence gut epithelial responses.
- To elucidate the signaling pathways involved in host-microbe interactions.
Main Methods:
- Analysis of host-pathogen interactions in a gut model.
- Investigated the role of uracil and the Hedgehog signaling pathway.
- Measured reactive oxygen species (ROS) production.
Main Results:
- Pathogen-secreted uracil was identified as a key molecule.
- Uracil acts at two distinct steps to induce ROS.
- The Hedgehog signaling pathway mediates uracil-induced ROS production.
Conclusions:
- Pathogen-secreted uracil is a critical factor in modulating gut epithelial defense.
- The Hedgehog pathway plays a role in integrating microbial signals to induce ROS.
- This mechanism contributes to the gut's ability to manage pathogen threats while tolerating commensals.
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