Resident intestinal eosinophils constitutively express antigen presentation markers and include two phenotypically distinct subsets of eosinophils

• Published in: Immunology 2018-06, Vol.154 (2), p.298-308
• Main Authors: Xenakis, Jason J., Howard, Emily D., Smith, Kalmia M., Olbrich, Courtney L., Huang, Yanjun, Anketell, Dilanjan, Maldonado, Samuel, Cornwell, Evangeline W., Spencer, Lisa A.
• Format: Article
• Language: English
• Subjects: Animals; Antigen presentation; Antigen Presentation - immunology; Antigen-presenting cells; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Biomarkers; Blood; eosinophil; eosinophilic gastrointestinal diseases; Eosinophils; Eosinophils - immunology; Eosinophils - metabolism; Eosinophils - pathology; Female; Fluorescence; Fluorescent Antibody Technique; Functional morphology; Green fluorescent protein; Immunophenotyping; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; intraepithelial; Intraepithelial Lymphocytes - immunology; Intraepithelial Lymphocytes - metabolism; Lamina propria; Leukocytes; Leukocytes (eosinophilic); Leukocytes - immunology; Leukocytes - metabolism; Localization; Markers; Membranes; Mice; Mice, Transgenic; mucosal immunity; non‐classical antigen presentation; Original; Phenotype; Phenotypes; Plasma membranes; Proteins; Small intestine
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12885

Summary Intestinal eosinophils are implicated in homeostatic and disease‐associated processes, yet the phenotype of intestinal tissue‐dwelling eosinophils is poorly defined and their roles in intestinal health or disease remain enigmatic. Here we probed the phenotype and localization of eosinophils constitutively homed to the small intestine of naive mice at baseline, and of antigen‐sensitized mice following intestinal challenge. Eosinophils homed to the intestinal lamina propria of naive mice were phenotypically distinguished from autologous blood eosinophils, and constitutively expressed antigen‐presenting cell markers, suggesting that intestinal eosinophils, unlike blood eosinophils, may be primed for antigen presentation. We further identified a previously unrecognized resident population of CD11chi eosinophils that are recovered with intraepithelial leucocytes, and that are phenotypically distinct from both lamina propria and blood eosinophils. To better visualize intestinal eosinophils in situ, we generated eosinophil reporter mice wherein green fluorescent protein expression is targeted to both granule‐delimiting and plasma membranes. Analyses of deconvolved fluorescent z‐section image stacks of intestinal tissue sections from eosinophil reporter mice revealed eosinophils within intestinal villi exhibited dendritic morphologies with cellular extensions that often contacted the basement membrane. Using an in vivo model of antigen acquisition in antigen‐sensitized mice, we demonstrate that both lamina propria‐associated and intraepithelium‐associated eosinophils encounter, and are competent to acquire, lumen‐derived antigen. Taken together these data provide new foundational insights into the organization and functional potential of intestinal tissue‐dwelling eosinophils, including the recognition of different subsets of resident intestinal eosinophils, and constitutive expression of antigen‐presenting cell markers. “Eosinophils are implicated in intestinal homeostasis and disease, yet the phenotype of intestinal tissue‐dwelling eosinophils is poorly defined and their roles in intestinal health or disease remain enigmatic. This study applies complementary flow cytometry and histopathological approaches in wild‐type and newly generated eosinophil reporter mice to investigate tissue‐resident eosinophils at baseline and after antigen sensitization and challenge. These data provide new foundational insights into the organization and functional potential o