Document Type

Article

Publication Date

4-2023

Identifier

DOI: 10.1016/j.mucimm.2023.02.002

Abstract

A key aspect of postnatal intestinal adaptation is the establishment of symbiotic relationships with co-evolved gut microbiota. Necrotizing enterocolitis (NEC) is the most severe disease arising from failure in postnatal gut adaptation in premature infants. Although pathological activation of intestinal Toll-like receptors (TLRs) is believed to underpin NEC pathogenesis, the mechanisms are incompletely understood. We postulate that unregulated aberrant TLR activation in NEC arises from a failure in intestinal-specific mechanisms that tamponade TLR signaling (the brakes). In this review, we discussed the human and animal studies that elucidate the developmental mechanisms inhibiting TLR signaling in the postnatal intestine (establishing the brakes). We then evaluate evidence from preclinical models and human studies that point to a defect in the inhibition of TLR signaling underlying NEC. Finally, we provided a framework for the assessment of NEC risk by screening for signatures of TLR signaling and for NEC prevention by TLR-targeted therapy in premature infants.

Journal Title

Mucosal Immunol

Volume

16

Issue

2

First Page

208

Last Page

220

MeSH Keywords

Infant; Animals; Infant, Newborn; Humans; Enterocolitis, Necrotizing; Infant, Premature; Toll-Like Receptors; Signal Transduction; Infant, Newborn, Diseases

Keywords

Necrotizing Enterocolitis; Toll-Like Receptors; Signal Transduction; Newborn Infant Diseases

Comments

This study was supported by institutional funds from Children’s Mercy Hospital (VS, AC), R01DK117296 (VS), and K08DK125735 (AC).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Publisher's Link: https://www.mucosalimmunology.org/article/S1933-0219(23)00010-7/fulltext

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