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Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.

Chu DK1, Jimenez-Saiz R1, Verschoor CP1, Walker TD1, Goncharova S1, Llop-Guevara A1, Shen P1, Gordon ME1, Barra NG1, Bassett JD1, Kong J1, Fattouh R2, McCoy KD3, Bowdish DM1, Erjefält JS4, Pabst O5, Humbles AA6, Kolbeck R6, Waserman S1, Jordana M7. J Exp Med. 2014 ;211(8):1657-72.

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1McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.and

2Clinical Microbiology, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5S 1A8, Canada.and

3Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3008 Bern, Switzerland.and

4Department of Experimental Medical Science, Lund University, SE-22184 Lund, Sweden Department of Respiratory Medicine and Allergology, Lund University Hospital, SE-22185 Lund, Sweden.and

5Institute of Molecular Medicine, RWTH Aachen University, 52074 Aachen, Germany.and

6Department of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, MA 20878.and

7McMaster Immunology Research Centre (MIRC), Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada [email protected]

 

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.

© 2014 Chu et al.

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Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo. . Global Medical Discovery

 

 

 

 

 

 

 

 

 

 

 

 

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