# Project 5

> **NIH NIH P20** · UNIVERSITY OF NORTH DAKOTA · 2020 · $287,893

## Abstract

SUMMARY:
Inflammatory disorders can be triggered by overactive immune responses directed against
host/self tissues. Indeed, neuroinflammation-associated disorders such as multiple sclerosis
and stroke can be triggered and/or exacerbated by overactive immune responses against
nervous tissues. It is now evident that not only cognitive disorders, but classic mental diseases
such as schizophrenia and depression, are related to neuroinflammation. It is thus remarkable
that infection with parasitic helminths (worms) suppresses inflammation in a variety of immune
disorders. Ongoing clinical trials using worm egg in patients with multiple sclerosis are showing
promising results. Hence, an understanding of helminth immunoregulatory mechanisms is likely
to have enormous impact on novel strategies against inflammatory disorders. In this light, the
regulation of inflammatory responses is mainly mediated via the innate immune system through
antigen-presenting cells (APC) such as macrophages (M�) and microglia (MG). The functional
phenotypes of MG and M� vary in response to external stimuli these cells receive through a
wide variety of surface receptors. It is thought that worms or their products induce alternatively
activated macrophages (AAM) that dampen inflammation and promotes tissue repair. We and
others have recently documented that alternatively activated M� (AA-M�) and MG (AA-MG)
have the capacity to dampen host inflammatory responses and promote wound healing and
tissue repair in certain chronic neuroinflammation-related diseases. In a mouse model of
neurocysticercosis (NCC) we demonstrated that AAMs are essential in containing
neuropathology and disease severity. Additionally, consistent with human NCC, highly antigenic
tegument galactose/ galactosamine and glucosamine containing glycan molecules of the
parasite are released and taken up by host cells in the CNS environment. As lectin receptors
(LRs) are the major receptors for recognition of glycan antigens, a study of their role in AA-M�
and AA-MG functions in the CNS during NCC are important for understanding how NCC and
neuropathological conditions can be clinically controlled. We hypothesize that glycan antigens
released by parasites will lead to differential expression of specific host LRs which will play a
critical role in the development and trafficking of AAM into the CNS, expression of effector
molecules, and regulation of CNS immunopathology. To test this hypothesis we propose 3
specific aims. (Aim 1) Determine the expression, kinetics, and cellular distribution of LRs during
NCC by focusing on Galectin-7, Galectin-9, and SIGNR1. (Aim 2) Identify the role of targeted
LRs in AA-M� and AA-MG development, migration and functions. (Aim 3) Elucidate the
significance of targeted LRs in regulating AA-M� and AA-MG mediated control of CNS
immunopathogenesis in murine NCC. Our findings in the planned studies are expected to
provide new directions and approaches to manipulate AA-M� and AA-MG functio...

## Key facts

- **NIH application ID:** 9924577
- **Project number:** 5P20GM113123-05
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** Bibhuti Bhusan Mishra
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $287,893
- **Award type:** 5
- **Project period:** — → 2021-08-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924577

## Citation

> US National Institutes of Health, RePORTER application 9924577, Project 5 (5P20GM113123-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9924577. Licensed CC0.

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