Suppression of inflammation and tissue damage by a hookworm recombinant protein in experimental colitis

Ferreira, Ivana B., Pickering, Darren A., Troy, Sally, Croese, John, Loukas, Alex, and Navarro, Severine (2017) Suppression of inflammation and tissue damage by a hookworm recombinant protein in experimental colitis. Clinical & Translational Immunology, 6. e157.

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Abstract

Gastrointestinal parasites, hookworms in particular, have evolved to cause minimal harm to their hosts when present in small numbers, allowing them to establish chronic infections for decades. They do so by creating an immunoregulatory environment that promotes their own survival, but paradoxically also benefits the host by protecting against the onset of many inflammatory diseases. To harness the therapeutic value of hookworms without using live parasites, we have examined the protective properties of the recombinant protein anti-inflammatory protein (AIP)-1, secreted in abundance by hookworms within the intestinal mucosa, in experimental colitis. Colitic inflammation assessed by weight loss, colon atrophy, oedema, ulceration and necrosis, as well as abdominal adhesion was significantly suppressed in mice treated with a single intraperitoneal dose of AIP-1 at 1 mg kg(-1). Local infiltration of inflammatory cells was also significantly reduced, with minimal goblet cell loss and preserved mucosal architecture. Treatment with AIP-1 promoted the production of colon interleukin (IL)-10, transforming growth factor (TGF)-beta and thymic stromal lymphopoietin (TSLP), resulting in the suppression of tumour necrosis factor (TNF)-alpha, IL-13 and IL-17 A cytokines and granulocyte macrophage colony-stimulating factor (GM-CSF), CX motif chemokine ( CXCL)-11 and cyclooxygenase synthase (COX)-2 mRNA transcripts. AIP-1 promoted the accumulation of regulatory T cells in the colon likely allowing rapid healing of the colon mucosa. Hookworm recombinant AIP-1 is a novel therapeutic candidate for the treatment of inflammatory bowel diseases that can be explored for the prevention of acute inflammatory relapses, an important cause of colorectal cancer.

Item ID: 51322
Item Type: Article (Research - C1)
ISSN: 2050-0068
Additional Information:

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0

Funders: National Health and Medical Research Council of Australia (NHMRC), Children's Hospital Foundation, James Cook University (JCU), Australian Institute of Tropical Health and Medicine (AITHM)
Projects and Grants: NHMRC grant 1037034
Date Deposited: 25 Oct 2017 07:37
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 80%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 100%
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