Indigenous Enteric Eosinophils Control DCs to Initiate a Primary Th2 Immune Response in vivo

Chu DK, Jimenez-Saiz R, Verschoor CP, Walker TD, Goncharova S, Llop-Guevara A, Shen P, Gordon ME, Barra NG, Bassett JD, Kong J, Fattouh R, McCoy KD, Bowdish DM, Erjefält JS, Pabst O, Humbles AA, Kolbeck R, Waserman S, Jordana M.

J Exp Med. 2014 Jul 28;211(8):1657-72. doi: 10.1084/jem.20131800.

Chu Picture

Front Row (Left to Right): Derek Chu, Manel Jordana Back Row (Left to Right): Rodrigo Jimenez-Saiz, Susanna Goncharova, Christopher Verschoor, Melissa Gordon, Tina Walker

The intestinal immune system is composed of a complex network of cells that must balance immunity and tolerance to ingested food antigens, pathogens, and the microbiota. Derangements in intestinal homeostasis lead to allergy, autoimmunity, and inflammatory bowel diseases. Although eosinophils have long been appreciated to be qualitatively abundant in the intestine, even in the absence of any pathology, a functional role for them there has remained elusive.

In this month’s Society of Mucosal Immunology Featured Paper, Indigenous Enteric Eosinophils Control DCs to Initiate a Primary Th2 Immune Resonse in vivo, Chu et al. shed light on “The curious case of the intestinal eosinophil.” First, the authors quantitated and analyzed eosinophils along the intestinal tract and showed that eosinophils are most abundant within the small intestine. To evaluate the contribution of intestinal eosinophils to mucosal immunity, the authors analyzed eosinophils in a model of peanut food allergy and anaphylaxis. In response to intestinal immunization with peanut allergen in vivo, intestinal eosinophils degranulated the molecule, eosinophil peroxidase (EPO), which activated local DCs to migrate to local lymph nodes to induce T cell priming and immunoglobulin production. These events were abolished in the absence of eosinophils and restored upon reconstitution with adoptive transfer of eosinophils, or generation of bone marrow chimeras involving eosinophils selectively deficient in IL-4. Lastly, extraintestinal priming with EPO also activated DCs and enhanced responses to OVA compared to priming with OVA alone.

Altogether, these data reveal the potential for intestinal eosinophils to make critical contributions to mucosal immunity. Interestingly, as opposed to the classical teaching that eosinophils are the end product of ongoing adaptive immunity, Chu et al. show that intestinal eosinophils can instead initiate adaptive immune responses. That this is achieved through cross-talk between resident eosinophils and DCs through degranulation of EPO also stresses the importance of cells neighbouring DCs in determining the immunological outcome to antigen exposure. Hence, intestinal eosinophils may play important roles in the pathogenesis or treatment of a number of immune mediated diseases such as allergy, autoimmunity, and inflammatory bowel disease. PubMed: 25071163