# Parasite immunity orchestrated by type 2 immune cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $403,750

## Abstract

Project Summary/Abstract
This grant seeks to understand the interactions between intestinal helminth infection and type 2 immune
responses that drive re-modeling of the intestinal epithelial barrier. Although type 2 immunity has been long-
associated with adaptive, chronic helminth intestinal infections, host protection is largely ineffective, and worms
continue to sustain egg-laying for months to years. The discovery of Group 2 innate lymphoid cells, or ILC2s,
by my group and others in 2010, opened new areas of research that uncovered physiologic processes
associated with type 2 immune cytokines relevant to metabolic and tissue homeostasis, suggesting the
alternative narrative that evolutionarily adapted parasites co-opt integral homeostatic pathways in order to
sustain chronic infection, access host nutrients, and preserve tissue integrity necessary to maintain
transmission of off-spring. In prior support from this grant, we discovered that tuft cells, rare mucosal epithelial
cells, are the source of IL-25, a key cytokine involved in activation of tissue ILC2s to release type 2 cytokines.
After intestinal helminth infection, mice activate lamina propria ILC2s to secrete IL-13, which alters progenitor
cell fate in intestinal crypts toward secretory cells, particularly tuft cells and goblet cells, thus identifying a
critical tuft cell – ILC2 circuit that integrates type 2 immunity with tissue homeostasis. In this renewal, we
propose to understand this circuit in order to be able to manipulate it in directions that curtail helminth infection
while preserving bowel integrity. The three Specific Aims involve defining the necessity for circuit activation to
sustain chronic parasitization; outlining the mechanisms underlying the small intestinal changes in physiology
that result from chronic circuit activation; and uncovering endogenous regulatory elements in the circuit that are
circumvented by parasites in order to maintain chronic activation of the tuft cell – ILC2 circuit. We believe that
understanding these basic pathways has great potential not only for control of parasitic helminthes, but also to
impact many diseases of intestinal dysfunction that remain of importance to humans.

## Key facts

- **NIH application ID:** 10144924
- **Project number:** 5R01AI026918-31
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Richard M Locksley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 1988-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144924

## Citation

> US National Institutes of Health, RePORTER application 10144924, Parasite immunity orchestrated by type 2 immune cells (5R01AI026918-31). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10144924. Licensed CC0.

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