title: Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.
abstract: Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Derek K
authors: DK
authors: Chu
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Rodrigo
authors: R
authors: Jimenez-Saiz
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Christopher P
authors: CP
authors: Verschoor
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Tina D
authors: TD
authors: Walker
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Susanna
authors: S
authors: Goncharova
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Alba
authors: A
authors: Llop-Guevara
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Pamela
authors: P
authors: Shen
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Melissa E
authors: ME
authors: Gordon
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Nicole G
authors: NG
authors: Barra
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Jennifer D
authors: JD
authors: Bassett
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Joshua
authors: J
authors: Kong
authors: Clinical Microbiology, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5S 1A8, Canada.
authors: Ramzi
authors: R
authors: Fattouh
authors: Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3008 Bern, Switzerland.
authors: Kathy D
authors: KD
authors: McCoy
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Dawn M
authors: DM
authors: Bowdish
authors: Department of Experimental Medical Science, Lund University, SE-22184 Lund, Sweden Department of Respiratory Medicine and Allergology, Lund University Hospital, SE-22185 Lund, Sweden.
authors: Jonas S
authors: JS
authors: Erjefält
authors: Institute of Molecular Medicine, RWTH Aachen University, 52074 Aachen, Germany.
authors: Oliver
authors: O
authors: Pabst
authors: Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, MA 20878.
authors: Alison A
authors: AA
authors: Humbles
authors: Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, MA 20878.
authors: Roland
authors: R
authors: Kolbeck
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Susan
authors: S
authors: Waserman
authors: McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada jordanam@mcmaster.ca.
authors: Manel
authors: M
authors: Jordana
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology* / Q000648:ultrastructure; D004921:Erythropoietin / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000166:cytology*; D006801:Humans; D007114:Immunization; D039001:Integrin alpha Chains / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039521:CD11c Antigen; D039001:Integrin alpha Chains; C091367:alpha E integrins; D004921:Erythropoietin; D015847:Interleukin-4