The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection.
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.
Dixon
Helen
H
Faculty of Life Sciences, University of Manchester, Manchester, UK. helen.dixon@manchester.ac.uk
Blanchard
Carine
C
Deschoolmeester
Matthew L
ML
Yuill
Nicola C
NC
Christie
Julie W
JW
Rothenberg
Marc E
ME
Else
Kathryn J
KJ
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
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D019409:Interleukin-15