Localization of the lipopolysaccharide recognition complex in the human healthy and inflamed premature and adult gut

Tim G A M Wolfs, Joep P M Derikx, Caroline M I M Hodin, Joris Vanderlocht, Ann Driessen, Adriaan P. De Bruine, Charles L Bevins, Felix Lasitschka, Nikolaus Gassler, Wim G. Van Gemert, Wim A. Buurman

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Background: Microbiota in the intestinal lumen provide an abundant source of potentially detrimental antigens, including lipopolysaccharide (LPS), a potent immunostimulatory product of Gram-negative bacteria recognized by the host via TLR-4 and MD-2. An aberrant immune response to LPS or other bacterial antigens has been linked to inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). Methods: We investigated which cells express MD-2 in the normal and inflamed ileum from neonates and adults by immunohistochemistry. Moreover, MD-2 and TLR4 mRNA expression in normal adult ileum was studied by reverse-transcription polymerase chain reaction (RT-PCR) on cells isolated by laser capture microdissection. Results: Premature infants did not show MD-2 expression either in epithelial cells or in the lamina propria. Similarly, MD-2 was absent in epithelial cells and lamina propria inflammatory cells in preterm infants with NEC. MD-2 protein in the healthy term neonatal and adult ileum was predominantly expressed by Paneth cells and some resident inflammatory cells in the lamina propria. MD-2 and TLR-4 mRNA expression was restricted to crypt cells. Also in IBD, Paneth cells were still the sole MD-2-expressing epithelial cells, whereas inflammatory cells (mainly plasma cells) were responsible for the vast majority of the MD-2 expression. Conclusions: The absence of MD-2 in the immature neonatal gut suggests impaired LPS sensing, which could predispose neonates to NEC upon microbial colonization of the immature intestine. The apparent expression of MD-2 by Paneth cells supports the critical concept that these cells respond to luminal bacterial products in order to maintain homeostasis with the intestinal microbiota in vivo.

Original languageEnglish (US)
Pages (from-to)68-75
Number of pages8
JournalInflammatory Bowel Diseases
Volume16
Issue number1
DOIs
StatePublished - Feb 2010

Keywords

  • Immunohistochemistry
  • Inflammatory bowel disease
  • Laser capture microdissection
  • MD-2
  • Necrotizing enterocolitis
  • TLR4

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

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