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 language | English |
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Pages (from-to) | 68-75 |
Number of pages | 8 |
Journal | Inflammatory Bowel Diseases |
Volume | 16 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2010 |
Keywords
- inflammatory bowel disease
- necrotizing enterocolitis
- TLR4
- MD-2
- immunohistochemistry
- laser capture microdissection
- INFLAMMATORY-BOWEL-DISEASE
- GRAM-NEGATIVE BACTERIA
- NECROTIZING ENTEROCOLITIS
- PANETH CELLS
- DENDRITIC CELLS
- SOLUBLE MD-2
- EXPRESSION
- PATHOGENESIS
- DEFENSINS