# Targeting professional APCs using Fasciola hepatica FABP to suppresses inflammation

> **NIH NIH SC1** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2020 · $360,250

## Abstract

ABSTRACT
 The growing use of `helminth-therapy' in the last decade to prevent or ameliorate inflammatory diseases is a
promising and novel approach. Fasciola hepatica, one of the most globally prevalent parasitic helminths of domestic
animals, is particularly adept at controlling the immune response of its host. At early stages of infection the parasite
induces a dominant Th2/T-regulatory-type immune response coincidental with suppression of Th1 responses.
Recent studies have demonstrated that F. hepatica infection attenuates the clinical signs of murine experimental
autoimmune encephalomyelitis [1] and prevents the development of Type-1 diabetes in a non-obese diabetic mouse
model [2]. However, the immunoregulation associated to F. hepatica lacks specificity and results in a compromised
immune system unable to respond effectively to bystander infections [3, 4]. A better alternative for drug
development would be to identify parasite molecules with immune-modulatory capacity and to characterize their
precise mechanism of action. Fatty acid binding proteins (FABPs) are proteins that play an important role in the
parasite's lipid metabolism and have been recently categorized as anti-oxidant molecules [5]. We have
demonstrated that a recombinant 14.5kDa protein belonging to the fatty acid binding protein (Fh15) is able to
significantly suppress the cytokine storm when is applied therapeutically 1h after exposure to lethal doses of LPS,
which suggest that Fh15 could act as a TLR4-antagonist. Moreover, we also found that Fh15-treatment increased
accumulation of large and small peritoneal MΦs (LPMs and SPMs) into the peritoneal cavity (PerC) compared to the
of septic mice [6]. Moreover, we also demonstrated by proximity ligation assay (PLA) that the native F. hepatica
FABP variant (Fh12) binds to the human CD14-coreceptor [7], which has been associated to the activation-signaling
cascade of various TLRs [8-11]. Because TLR4 is directly involved in the inflammatory responses during sepsis and
ulcerative colitis (UC), this role for Fh15 could have a significant impact on human health [12, 13]. Our central
hypothesis is that the suppression of pro-inflammatory cytokines induced by injection (i.p.) with Fh15 is enough to
prevent the high mortality in mice exposed to a lethal dose of LPS and to prevent or ameliorate the intestinal
inflammation in a DSS-induced mouse model of UC. Both therapeutic effects will be directly associated with the
production of M2-type MΦs in the PerC of animals and the induction of tolerogenic properties of DCs, which will be
critically dependent on CD14. The proposed research is conceptually innovative because it is the first time that a
protein of the F. hepatica FABP family, specifically Fh15, is investigated as an anti-inflammatory molecule and there
are no reported works on MΦs and DCs in relation to Fh15 exposure in vivo or in vitro. Understanding how Fh15
modulate and interact with MΦs and DCs at early stages of innate immun...

## Key facts

- **NIH application ID:** 9936534
- **Project number:** 1SC1AI155439-01
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** ANA M ESPINO
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $360,250
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936534

## Citation

> US National Institutes of Health, RePORTER application 9936534, Targeting professional APCs using Fasciola hepatica FABP to suppresses inflammation (1SC1AI155439-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9936534. Licensed CC0.

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