# The Notch Signaling Pathway Regulates Basophil Responses During Helminth Infection

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $441,250

## Abstract

PROJECT SUMMARY
Intestinal helminth parasites infect millions of people worldwide and cause significant morbidity. Host-
protective type 2 inflammation is characterized by activation of innate immune cells, polarization of naïve CD4+
T cells to T helper type 2 cells, anti-helminth epithelial cell responses, and worm expulsion. Recent studies
have revealed that basophils, rare innate granulocytes, promote type 2 inflammation and worm expulsion, but
the pathways that control basophil effector function following helminth infection remain incompletely defined.
However, the Notch signaling pathway stands out as a key candidate that could regulate basophil responses in
this context. Ligand binding to a Notch receptor leads to nuclear translocation of the Notch intracellular
domain, which can promote transcriptional activation of canonical type 2 inflammation-associated target genes
and the development of type 2 inflammatory responses. However, how Notch shapes basophil responses that
regulate intestinal type 2 inflammation and helminth expulsion in vivo is unknown. To address this, in
preliminary studies, we show for the first time that murine basophils expressed Notch 2 following infection with
the intestinal helminth parasite Trichuris muris. Using mice in which Notch signaling is genetically blocked
solely in basophils, we demonstrate that while Notch signaling was not required to maintain the basophil
population in the steady state, it does contribute to optimal basophil population expansion and helminth
clearance following T. muris infection. Finally, we show that Notch signaling regulates cytokine-elicited
basophil activation in vitro. Collectively, these data led us to hypothesize that during intestinal helminth
parasite infection, basophils upregulate Notch and respond to Notch ligands, mediating optimal basophil
population expansion and effector function and efficient helminth expulsion. To test this, we propose three
specific aims. Studies in Aim 1 will test how the Notch signaling pathway regulates basophil population
expansion and differentiation during type 2 inflammation, employing in vitro assays and in vivo approaches
during T. muris infection. Studies in Aim 2 will test how Notch signaling promotes basophil effector function
and contributions to type 2 inflammation in vivo using adoptive transfer studies and infection with T. muris, with
some studies focusing on the role of Notch 2 in this process. Studies in Aim 3 will test how Notch ligands or
helminth proteases could activate Notch signaling in basophils to promote effector function and type 2
inflammation, using in vivo experiments during T. muris infection and in vitro assays. These studies will dissect
how Notch signaling regulates basophil responses that drive type 2 inflammation in the intestine following
helminth parasite infection. Our results will expand our understanding of intestinal type 2 inflammation and
inform the development and use of therapies that target Notch to t...

## Key facts

- **NIH application ID:** 9962283
- **Project number:** 5R01AI132708-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Elia D Tait Wojno
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $441,250
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962283

## Citation

> US National Institutes of Health, RePORTER application 9962283, The Notch Signaling Pathway Regulates Basophil Responses During Helminth Infection (5R01AI132708-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9962283. Licensed CC0.

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