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

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 antigen...

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Hauptverfasser: Wolfs, Tim (VerfasserIn) , Derikx, Joep P.M. (VerfasserIn) , Hodin, Caroline M.I.M. (VerfasserIn) , Vanderlocht, Joris (VerfasserIn) , Driessen, Ann (VerfasserIn) , Bruïne, Adriaan P. de (VerfasserIn) , Bevins, Charles L. (VerfasserIn) , Lasitschka, Felix (VerfasserIn) , Gassler, Nikolaus (VerfasserIn) , Gemert, Wim G. vaon (VerfasserIn) , Buurman, Wim A. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 1 January 2010
In: Inflammatory bowel diseases
Year: 2010, Jahrgang: 16, Heft: 1, Pages: 68-75
ISSN:1536-4844
DOI:10.1002/ibd.20995
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/ibd.20995
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Verfasserangaben:Tim G.A.M. Wolfs, Joep P.M. Derikx, Caroline M.I.M. Hodin, Joris Vanderlocht, Ann Driessen, Adriaan P. de Bruïne, Charles L. Bevins, Felix Lasitschka, Nikolaus Gassler, Wim G. van Gemert, and Wim A. Buurman

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520 |a 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).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.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.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. (Inflamm Bowel Dis 2010;) 
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