Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice

Chunxian Zhang; Michael P Sherman; Lawrence S Prince; David Bader; Jörn-Hendrik Weitkamp; James C Slaughter; Steven J McElroy

doi:10.1242/dmm.009001

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Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice

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Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice

Chunxian Zhang, Michael P Sherman, Lawrence S Prince, David Bader, Jörn-Hendrik Weitkamp, James C Slaughter and Steven J McElroy

Disease models & mechanisms, Vol.5(4), pp.522-532

07/2012

DOI: 10.1242/dmm.009001

PMCID: PMC3380715

PMID: 22328592

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Abstract

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. During NEC pathogenesis, bacteria are able to penetrate innate immune defenses and invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Normally, Paneth cells appear in the intestinal crypts during the first trimester of human pregnancy. Paneth cells constitute a major component of the innate immune system by producing multiple antimicrobial peptides and proinflammatory mediators. To better understand the possible role of Paneth cell disruption in NEC, we quantified the number of Paneth cells present in infants with NEC and found that they were significantly decreased compared with age-matched controls. We were able to model this loss in the intestine of postnatal day (P)14-P16 (immature) mice by treating them with the zinc chelator dithizone. Intestines from dithizone-treated animals retained approximately half the number of Paneth cells compared with controls. Furthermore, by combining dithizone treatment with exposure to Klebsiella pneumoniae , we were able to induce intestinal injury and inflammatory induction that resembles human NEC. Additionally, this novel Paneth cell ablation model produces NEC-like pathology that is consistent with other currently used animal models, but this technique is simpler to use, can be used in older animals that have been dam fed, and represents a novel line of investigation to study NEC pathogenesis and treatment.

Details

Title: Subtitle: Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice
Creators: Chunxian Zhang - Departments of Pediatrics
Michael P Sherman - Department of Child Health, University of Missouri Health System, Columbia, MO 65201, USA
Lawrence S Prince - Departments of Pediatrics
David Bader - Cardiovascular Medicine and
Jörn-Hendrik Weitkamp - Departments of Pediatrics
James C Slaughter - Biostatistics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Steven J McElroy - Departments of Pediatrics
Resource Type: Journal article
Publication Details: Disease models & mechanisms, Vol.5(4), pp.522-532
DOI: 10.1242/dmm.009001
PMID: 22328592
PMCID: PMC3380715
NLM abbreviation: Dis Model Mech
ISSN: 1754-8403
eISSN: 1754-8411
Publisher: The Company of Biologists Limited
Language: English
Date published: 07/2012
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics
Record Identifier: 9984093214602771

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