title: Hookworm excretory/secretory products induce interleukin-4 (IL-4)+ IL-10+ CD4+ T cell responses and suppress pathology in a mouse model of colitis.
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.
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Queensland Tropical Health Alliance, James Cook University, Cairns, Queensland, Australia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ferreira
authors.forename: Danielle
authors.initials: D
authors.lastname: Smyth
authors.forename: Soraya
authors.initials: S
authors.lastname: Gaze
authors.forename: Ammar
authors.initials: A
authors.lastname: Aziz
authors.forename: Paul
authors.initials: P
authors.lastname: Giacomin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ruyssers
authors.forename: David
authors.initials: D
authors.lastname: Artis
authors.forename: Thewarach
authors.initials: T
authors.lastname: Laha
authors.forename: Severine
authors.initials: S
authors.lastname: Navarro
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McSorley
mesh_terms: D000722:Ancylostoma / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D003106:Colon / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004804:Eosinophils / Q000166:cytology; D005260:Female; D015801:Helminth Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology
chemical_list: D016207:Cytokines; D015801:Helminth Proteins; C556062:IL10 protein, mouse; D016753:Interleukin-10; D015847:Interleukin-4; D016264:Dextran Sulfate
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