Yeshi, Karma, Ruscher, Roland, Loukas, Alex, and Wangchuk, Phurpa (2022) Immunomodulatory and biological properties of helminth-derived small molecules: Potential applications in diagnostics and therapeutics. Frontiers in Parasitology, 1. 984152.

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Abstract

Parasitic helminths secrete and excrete a vast array of molecules known to help skew or suppress the host’s immune response, thereby establishing a niche for sustained parasite maintenance. Indeed, the immunomodulatory potency of helminths is attributed mainly to excretory/secretory products (ESPs). The ESPs of helminths and the identified small molecules (SM) are reported to have diverse biological and pharmacological properties. The available literature reports only limited metabolites, and the identity of many metabolites remains unknown due to limitations in the identification protocols and helminth-specific compound libraries. Many metabolites are known to be involved in host-parasite interactions and pathogenicity. For example, fatty acids (e.g., stearic acid) detected in the infective stages of helminths are known to have a role in host interaction through facilitating successful penetration and migration inside the host. Moreover, excreted/secreted SM detected in helminth species are found to possess various biological properties, including anti-inflammatory activities, suggesting their potential in developing immunomodulatory drugs. For example, helminths-derived somatic tissue extracts and whole crude ESPs showed anti-inflammatory properties by inhibiting the secretion of proinflammatory cytokines from human peripheral blood mononuclear cells and suppressing the pathology in chemically-induced experimental mice model of colitis. Unlike bigger molecules like proteins, SM are ideal candidates for drug development since they are small structures, malleable, and lack immunogenicity. Future studies should strive toward identifying unknown SM and isolating the under-explored niche of helminth metabolites using the latest metabolomics technologies and associated software, which hold potential keys for finding new diagnostics and novel therapeutics.

Item ID:	76055
Item Type:	Article (Research - C1)
ISSN:	2813-2424
Keywords:	helminths, immunomodulatory, small molecules, excretory-secretory products, biological activities, pharmacological properties, metabolomics
Copyright Information:	Copyright © 2022 Yeshi, Ruscher, Loukas and Wangchuk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Funders:	National Health and Medical Research Council (NHMRC)
Projects and Grants:	NHMRC Ideas Grant (APP1183323), NHMRC Program Grant (APP1132975), NHMRC Senior Principal Research Fellowship (APP1117504)
Date Deposited:	14 Sep 2022 23:48
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320599 Medical biochemistry and metabolomics not elsewhere classified @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321402 Clinical pharmacology and therapeutics @ 50%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280105 Expanding knowledge in the chemical sciences @ 50% 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 50%
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