Ferreira, I. et al. (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), pp. 2104-2111. (doi: 10.1128/IAI.00563-12) (PMID:23545299) (PMCID:PMC3676036)
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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.
| Item Type: | Articles |
|---|---|
| Additional Information: | This study was supported by a National Health and Medical Research Council of Australia (NHMRC) program grant. I.F. was supported by an Australian Postgraduate Award. D.S. was supported by a Human Frontiers in Science Program Short Term Fellowship. A.L. was supported by a principal research fellowship from the NHMRC. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Smyth, Dr Danielle |
| Authors: | Ferreira, I., Smyth, D., Gaze, S., Aziz, A., Giacomin, P., Ruyssers, N., Artis, D., Laha, T., Navarro, S., Loukas, A., and McSorley, H. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Infection and Immunity |
| Publisher: | American Society for Microbiology |
| ISSN: | 0019-9567 |
| ISSN (Online): | 1098-5522 |
| Published Online: | 01 April 2013 |
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