Impact of Toll-Like Receptor 4 Signaling in Necrotizing Enterocolitis: The State of the Science

Clin Perinatol. 2019 Mar;46(1):145-157. doi: 10.1016/j.clp.2018.09.007. Epub 2018 Dec 20.

Abstract

Necrotizing enterocolitis (NEC) remains a leading cause of preterm infant mortality. NEC is multifactorial and believed a consequence of intestinal immaturity, microbial dysbiosis, and an exuberant inflammatory response. Over the past decade, exaggerated Toll-like receptor 4 (TLR4) activity in the immature intestine of preterm neonates emerged as an inciting event preceding NEC. Increased TLR4 signaling in epithelial cells results in the initiation of an uncontrolled immune response and destruction of the mucosal barrier. This article discusses the state of the science of the molecular mechanisms involved in TLR4-mediated inflammation during NEC and the development of new therapeutic strategies to prevent NEC.

Keywords: Epithelial cells; Inflammation; Necrotizing enterocolitis; TLR4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Enterocolitis, Necrotizing / immunology*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Inflammation / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Toll-Like Receptor 4 / immunology*

Substances

  • TLR4 protein, human
  • Toll-Like Receptor 4