Hookworm excretory/secretory products induce interleukin-4 (il-4)+ il-10+ cd4+ t cell responses and suppress pathology in a mouse model of colitis

Ivana Ferreira, Danielle Smyth, Soraya Gaze, Ammar Aziz, Paul Giacomin, Nathalie Ruyssers, David Artis, Thewarach Laha, Severine Navarro, Alex Loukas, Henry J. McSorleya

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Evidence from human studies and mouse models shows that infection with parasitic helminths has a suppressive effect on the pathogenesis of some inflammatory diseases. Recently, we and others have shown that some of the suppressive effects of hookworms reside in their excretory/secretory (ES) products. Here, we demonstrate that ES products of the hookworm Ancylostoma caninum (AcES) suppress intestinal pathology in a model of chemically induced colitis. This suppression was associated with potent induction of a type 2 cytokine response characterized by coexpression of interleukin-4 (IL-4) and IL-10 by CD4+ T cells, downregulation of proinflammatory cytokine expression in the draining lymph nodes and the colon, and recruitment of alternatively activated (M2) macrophages and eosinophils to the site of ES administration. Protease digestion and heat denaturation of AcES resulted in impaired induction of CD4+ IL-4+ IL-10+ cell responses and diminished ability to suppress colitis, indicating that protein component(s) are responsible for some of the immunosuppressive effects of AcES. Identification of the specific parasite- derived molecules responsible for reducing pathology during chemically induced colitis could lead to the development of novel therapeutics for the treatment of human inflammatory bowel disease.

Original languageEnglish
Pages (from-to)2104-2111
Number of pages8
JournalInfection and Immunity
Volume81
Issue number6
DOIs
Publication statusPublished - 1 Jun 2013

Fingerprint Dive into the research topics of 'Hookworm excretory/secretory products induce interleukin-4 (il-4)<sup>+</sup> il-10<sup>+</sup> cd4<sup>+</sup> t cell responses and suppress pathology in a mouse model of colitis'. Together they form a unique fingerprint.

  • Cite this

    Ferreira, I., Smyth, D., Gaze, S., Aziz, A., Giacomin, P., Ruyssers, N., Artis, D., Laha, T., Navarro, S., Loukas, A., & McSorleya, H. J. (2013). Hookworm excretory/secretory products induce interleukin-4 (il-4)+ il-10+ cd4+ t cell responses and suppress pathology in a mouse model of colitis. Infection and Immunity, 81(6), 2104-2111. https://doi.org/10.1128/IAI.00563-12