# Genetic determinants of parasitic nematode tissue tropism and immune sensing

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $194,375

## Abstract

7. Project Summary/Abstract
Parasitic nematodes continue to cause significant morbidity and mortality in humans and animals on a global
scale. Central to their virulence is the ability to infect specific tissues and to evade and/or subvert the host’s
immune response. A better understanding of the molecules and pathways triggered by the nematode parasite
that govern its survival and migration through the host could allow identification of new therapeutic targets for
nematode infection. It is widely recognized that helminth immune modulation and the pathology they cause is
largely effected through the release of proteins and small molecules that interact with host cells and tissues,
and that these molecules are key factors in tissue tropism. Previous and current helminth secretome and
excreted/secreted protein (ESP) studies have been done in vitro, due to the difficulty of obtaining large
volumes of ESPs from small helminth parasites. However, there has been no rigorous validation that the in
vitro induction of ESPs mimics in vivo conditions. Additionally, the effects of host immune pressure on
expression of ESPs and other nematode genes are unknown. To fill these current gaps in knowledge, we
propose to perform high resolution transcriptomic profiling at the single nematode level of Nippostrongylus
brasiliensis throughout its life cycle in a genetically susceptible or resistant rodent host. We will profile the
transcription of parasites as they transition from free-living to being actively parasitic, and as they infect the
lung and the intestine. N. brasiliensis is in the order Strongylida, closely related to hookworm, and it shares
many life cycle features with hookworm, such as skin penetration, infection of the lungs, and infection of the
intestine. Data from this project will provide stage-specific gene signatures that are associated with the tissue
tropism of hookworms and determine how they are influenced by host immune pressure. Our proposed study
will test the assumption that i) intestinal nematodes initiate specific genetic programs and ESPs that determine
tissue tropism; ii) the context of host immune pressure affects parasite transcriptional programs. Further, by
comparing transcriptional profiles of nematodes under in vivo culture conditions and comparing them to
nematodes under in vitro conditions, we can directly test the assumption that in vitro conditions mimic in vivo
infection. Data generated will lay the foundation for future studies on helminth tissue tropism, ESPs, and
immune-targeted helminth pathways.

## Key facts

- **NIH application ID:** 9824547
- **Project number:** 5R21AI142121-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Adler Ray Dillman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2018-11-16 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9824547

## Citation

> US National Institutes of Health, RePORTER application 9824547, Genetic determinants of parasitic nematode tissue tropism and immune sensing (5R21AI142121-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9824547. Licensed CC0.

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