# An Immune Surveillance Network in C. elegans

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $418,750

## Abstract

PROJECT SUMMARY
An evolutionarily ancient strategy to activate innate immune defenses involves monitoring for changes in
cellular physiology, rather than the presence of pathogens themselves. Key insights into these mechanisms
have come from studies in the nematode C. elegans, which consume bacteria for food, and rely on
“surveillance immunity” to discriminate pathogens from potential food sources. Although several elegant
examples of surveillance immunity have been described, the host proteins that sense intracellular pathogen-
associated ligands to activate protective host responses are not known. As a critical first step to solving this
problem, we have identified a cellular surveillance network that coordinates immune effector induction in C.
elegans. These data offer a new paradigm of how immune pathways are activated in the intestinal epithelial
cells of a metazoan host. The central hypothesis of this proposal is that a surveillance network composed of
nuclear hormone receptors (NHRs) functions an intracellular monitor for small molecule toxins (or their
effects) and engages protective immune responses. In support of this hypothesis, we have made several key
observations that provide the rationale for the proposed work: (i) An immunostimulatory small molecule called
R24 causes the robust induction of immune effectors via a mechanism that is distinct from known innate
immune pathways, but is dependent on the conserved transcriptional regulator MDT-15/MED15. (ii) A single
NHR is the central regulator in a cellular network that surveys intestinal epithelial cells for xenobiotic toxins.
We have shown that this NHR drives the induction of protective defense responses by physically interacting
with MDT-15. (iii) A specific fatty acid, whose synthesis is regulated by MDT-15, is required for the induction
of immune defenses. In this proposal, we will characterize a surveillance network that activates immune
defenses following toxin exposure (Aim 1). We will define the role of the fatty acid signal in controlling
immune activation (Aim 2). We will determine whether the immune surveillance network acts locally within
intestinal epithelial cells or systemically in mediating pathogen defense (Aim 3). Mechanisms of surveillance
immunity are among the most primitive forms of pathogen detection in metazoans, and are conserved in
humans. Thus, it is our expectation that insights from these studies in C. elegans will reveal evolutionary
conserved strategies of immune activation, toxin recognition and cellular homeostasis in mammalian
immunity.

## Key facts

- **NIH application ID:** 10158394
- **Project number:** 5R01AI130289-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Read Pukkila-Worley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2017-06-22 → 2022-06-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158394

## Citation

> US National Institutes of Health, RePORTER application 10158394, An Immune Surveillance Network in C. elegans (5R01AI130289-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10158394. Licensed CC0.

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