Abstract

Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This was associated with changes in the production of enteric signals that regulate eosinophil attraction and survival, and was fully reversed by complex colonization. Additionally, SI eosinophils of GF mice exhibited more cytoplasmic protrusions and less granule content than SPF controls. Lastly, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate, and adaptive immune processes in health and disease.

Highlights

  • Eosinophils have traditionally been described as effector inflammatory cells that are protective against parasitic infections but detrimental in allergic disease [1, 2]

  • New evidence has established that eosinophils contribute to the initiation, propagation, and resolution of innate and adaptive immune responses, and to homeostatic tissue repair and remodeling [4, 5, 64, 65]

  • Given that eosinophils natively inhabit the small intestinal (SI) [66], we investigated the impact of the microbiota on intestinal eosinophil frequency and function

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Summary

Introduction

Eosinophils have traditionally been described as effector inflammatory cells that are protective against parasitic infections but detrimental in allergic disease [1, 2]. New evidence has considerably broadened this paradigm as eosinophils have been shown to play complex roles in mucosal immunity and tissue remodeling [3,4,5,6,7,8]. Intestinal accumulation of eosinophils has been associated with the severity of inflammatory bowel disease (IBD) [10, 11]. Eosinophils have been proposed to play a role in homeostatic tissue remodeling as Microbial Regulation of Enteric Eosinophils their presence is increased at tissues with a high turnover such as the intestine and the uterus [4, 14]. Deciphering the factors that regulate eosinophils in the GI mucosa is relevant to understanding their role in health and disease

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