Microbial regulation of enteric eosinophils and its impact on tissue remodeling and Th2 immunity

Abstract

23Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the 24 impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, 25we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that 26 small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to 27 specific pathogen free (SPF) controls. This was associated with changes in the production of enteric 28 signals that regulate eosinophil attraction and survival, and was fully reversed by complex 29 colonization. Additionally, SI eosinophils of GF mice exhibited more cytoplasmic protrusions and 30 less granule content than SPF controls. Lastly, we generated a novel strain of eosinophil-deficient 31 GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as 32 compared to GF controls. Overall, our study demonstrates that commensal microbes regulate 33intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization 34 to food antigens. These data support a critical interplay between the commensal microbiota and 35

EAACI Biologicals Guidelines—Recommendations for severe asthma

“…In healthy individuals, eosinophils contribute to protective immune responses directed against parasites, viral, bacterial and fungal pathogens, are crucial for the survival of long‐lived plasma cells and are critical regulators of local immunity and remodelling/repair in both health and disease 191,192 . Homeostatic eosinophils present in healthy individuals in various tissues are related to the control of glucose homeostasis, protection against obesity, regulation of mammary gland development, preparation of the uterus for pregnancy and the maintenance of the intestinal homeostasis in collaboration with the local microbiota 193–196 . In the lung, homeostatic eosinophils have been shown to suppress T2‐driven airway responses 197 …”

“…191,192 Homeostatic eosinophils present in healthy individuals in various tissues are related to the control of glucose homeostasis, protection against obesity, regulation of mammary gland development, preparation of the uterus for pregnancy and the maintenance of the intestinal homeostasis in collaboration with the local microbiota. [193][194][195][196] In the lung, homeostatic eosinophils have been shown to suppress T2-driven airway responses. 197 Besides its role against parasites, IgE can exert anti-neoplastic surveillance via mast cell and eosinophil-mediated cytotoxicity or by engaging and re-educating alternatively activated macrophages towards pro-inflammatory phenotypes and by priming all subsets to mediate anti-tumour functions.…”

Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity

“…We thank all the members of the Jordana Lab for technical help and scientific input. This manuscript has been released as a Pre-Print at bioRxiv (78).…”

Small Intestinal Resident Eosinophils Maintain Gut Homeostasis Following Microbial Colonisation

“…Out of all the homeostatic organs where tissue-resident eosinophils are found, the gastrointestinal tract harbours the largest population. They are recruited during late gestation and in early life in a manner independent of the microbiota (Jimenez-Saiz et al, 2020; Mishra et al, 1999). Recent studies have provided evidence for an important role of resident eosinophils in immunoregulation and maintenance of immune populations in the gastrointestinal tract, particularly in the small intestine (SI), both during homeostasis (Chu et al, 2014b; Jung et al, 2015; Sugawara et al, 2016) and upon bacterial infection (Arnold et al, 2018; Buonomo et al, 2016).…”