title: CCR3 is required for tissue eosinophilia and larval cytotoxicity after infection with Trichinella spiralis.
abstract: The CCR3 binds at least seven different CC chemokines and is expressed on eosinophils, mast cells (MC), and a subset of Th cells (Th2) that generate cytokines implicated in mucosal immune responses. Using mice with a targeted disruption of CCR3 (CCR3(-/-)) and their +/+ littermates, we investigated the role of CCR3 in the amplification of tissue eosinophilia and MC hyperplasia in the mouse after infection with Trichinella spiralis. In CCR3(-/-) mice, eosinophils are not recruited to the jejunal mucosa after infection and are not present in the skeletal muscle adjacent to encysting larvae. In addition, the number of cysts in the skeletal muscle is increased and the frequency of encysted larvae exhibiting necrosis is reduced. The CCR3(-/-) mice exhibit the expected MC hyperplasia in the jejunum and caecum and reject the adult worms from the small intestine at a normal rate. This study is consistent with distinct functions for MC (adult worm expulsion) and eosinophils (toxicity to larvae) in immunity to a helminth, T. spiralis, and defines the essential requirement for CCR3 in eosinophil, but not MC recruitment to tissues.
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. mgurish@rics.bwh.harvard.edu
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gurish
authors.forename: Alison
authors.initials: A
authors.lastname: Humbles
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.forename: Stella
authors.initials: S
authors.lastname: Finkelstein
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Boyce
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Friend
authors.forename: K Frank
authors.initials: KF
authors.lastname: Austen
mesh_terms: D000818:Animals; D004802:Eosinophilia / Q000209:etiology*; D007814:Larva / Q000276:immunology; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology; D017160:Trichinella spiralis / Q000276:immunology* / Q000469:parasitology; D014235:Trichinellosis / Q000276:immunology* / Q000473:pathology
chemical_list: C515351:Ccr3 protein, mouse; D054397:Receptors, CCR3; D019707:Receptors, Chemokine