Peptides derived from hookworm anti-inflammatory proteins suppress inducible colitis in mice and inflammatory cytokine production by human cells

Claudia Cobos; Paramjit S Bansal; David T Wilson; Linda Jones; Guangzu Zhao; Matthew A Field; Ramon M Eichenberger; Darren A Pickering; Rachael Y M Ryan; Champa N Ratnatunga; John J Miles; Roland Ruscher; Paul R Giacomin; Severine Navarro; Alex Loukas; Norelle L Daly

doi:10.3389/fmed.2022.934852

Peptides derived from hookworm anti-inflammatory proteins suppress inducible colitis in mice and inflammatory cytokine production by human cells

Front Med (Lausanne). 2022 Sep 9:9:934852. doi: 10.3389/fmed.2022.934852. eCollection 2022.

Authors

Claudia Cobos¹, Paramjit S Bansal¹, David T Wilson¹, Linda Jones¹, Guangzu Zhao¹, Matthew A Field^{1

2

3}, Ramon M Eichenberger¹, Darren A Pickering¹, Rachael Y M Ryan¹, Champa N Ratnatunga¹, John J Miles¹, Roland Ruscher¹, Paul R Giacomin¹, Severine Navarro^{1

4

5}, Alex Loukas¹, Norelle L Daly¹

Affiliations

¹ Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
² Centre for Tropical Bioinformatics and Molecular Biology, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
³ Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁴ Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁵ Faculty of Health, Woolworths Centre for Childhood Nutrition Research, Queensland University of Technology, South Brisbane, QLD, Australia.

Abstract

A decline in the prevalence of parasites such as hookworms appears to be correlated with the rise in non-communicable inflammatory conditions in people from high- and middle-income countries. This correlation has led to studies that have identified proteins produced by hookworms that can suppress inflammatory bowel disease (IBD) and asthma in animal models. Hookworms secrete a family of abundant netrin-domain containing proteins referred to as AIPs (Anti-Inflammatory Proteins), but there is no information on the structure-function relationships. Here we have applied a downsizing approach to the hookworm AIPs to derive peptides of 20 residues or less, some of which display anti-inflammatory effects when co-cultured with human peripheral blood mononuclear cells and oral therapeutic activity in a chemically induced mouse model of acute colitis. Our results indicate that a conserved helical region is responsible, at least in part, for the anti-inflammatory effects. This helical region has potential in the design of improved leads for treating IBD and possibly other inflammatory conditions.

Keywords: colitis mouse model; inflammation; nuclear magnetic resonance; peptide synthesis; protein structure.