Hookworms
secrete a barrage of Excretory/Secretory molecules (ES) into the mammalian
host’s gut mucosa to assist in blood-feeding and evasion of the host’s immune
response. ES products of the hookworm, Ancylostoma caninum, are therefore of
interest as a source of therapeutic molecules for treating inflammatory
disorders [1]. To date, hookworm ES proteins >10 kDa have
been characterized using proteomics techniques,[2] and have displayed efficacy in suppressing
inflammation associated with mouse models of colitis[3]. Some of the ES proteins responsible for
suppressing inflammation have been identified and shown to protect against
chemical colitis[4]. Much of the amino acid content of hookworm ES
products is associated with as yet characterized low molecular weight
peptides that pass through 10 kDa cut-off membranes but this material has not
yet been characterized at the molecular level. Small peptides and compounds of
less than 10 kDa are capable of acting in roles as diverse as signal
transduction, immunomodulation and hormone-driven processes. In this
investigation we carried out a shotgun proteomic analysis of the low molecular
weight ES products secreted by A. caninum
and show that defined fractions separated by RP-HPLC protect mice against TNBS
colitis. Future work will identify the protective moieties and produce them in
synthetic form for further trials. We have shown that hookworm secreted peptides
possess anti-inflammatory properties and reveals their potential as a source of
novel therapeutic compounds.
- Navarro, S., I. Ferreira, and A. Loukas, The hookworm pharmacopoeia for inflammatory diseases. Int J Parasitol, 2013. 43(3-4): p. 225-31
- Mulvenna, J., et al., Proteomics analysis of the excretory/secretory component of the blood-feeding stage of the hookworm, Ancylostoma caninum. Mol Cell Proteomics, 2009. 8(1): p. 109-21.
- Ruyssers, N.E., et al., Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis, 2009. 15(4): p. 491-500.
- Ferreira, I., et al., Hookworm Excretory/Secretory Products Induce Interleukin-4 (IL-4)+ IL-10+ CD4+ T Cell Responses and Suppress Pathology in a Mouse Model of Colitis. Infect Immun, 2013. 81(6): p. 2104-11.