title: The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection.
abstract: Trichinella spiralis and Trichuris muris are nematode parasites of the mouse, dwelling in the small and large intestines, respectively: worm expulsion requires development of a Th2 immune response. The chemokine CCL11 is agonist for the chemokine receptor CCR3 and acts in synergy with IL-5 to recruit eosinophils to inflammatory sites. The role of CCL11 in gastrointestinal helminth infection has not been previously studied. We challenged wild-type (WT) BALB/c, CCL11 single knockout (SKO) and CCL11 IL-5 double knockout (DKO) mice with either T. spiralis muscle larvae or T. muris eggs in order to examine eosinophil recruitment to the small and large intestine during helminth infection. A peripheral eosinophilia was seen in WT and SKO mice during T. spiralis infection but not with T. muris. Gastrointestinal eosinophilia was markedly reduced but not ablated in SKO mice -- and negligible in DKO mice -- infected with either nematode. The residual eosinophilia and up-regulation of CCL24 mRNA in the gastrointestinal tract of SKO mice infected with either nematode, together with the presence of an eosinophil-active factor in T. spiralis and T. muris products, suggest that CCL11 is the salient but not the sole eosinophil chemoattractant of biological significance during gastrointestinal helminth infection.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK. helen.dixon@manchester.ac.uk
authors.forename: Helen
authors.initials: H
authors.lastname: Dixon
authors.forename: Carine
authors.initials: C
authors.lastname: Blanchard
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Deschoolmeester
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Yuill
authors.forename: Julie W
authors.initials: JW
authors.lastname: Christie
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Else
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005753:Gastric Mucosa / Q000276:immunology* / Q000469:parasitology; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D017160:Trichinella spiralis / Q000276:immunology; D014235:Trichinellosis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D014257:Trichuriasis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D014258:Trichuris / Q000276:immunology
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D019409:Interleukin-15