title: Localization of the lipopolysaccharide recognition complex in the human healthy and inflamed premature and adult gut.
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.
authors.affiliation: Department of Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Tim G A M
authors.initials: TG
authors.lastname: Wolfs
authors.forename: Joep P M
authors.initials: JP
authors.lastname: Derikx
authors.forename: Caroline M I M
authors.initials: CM
authors.lastname: Hodin
authors.forename: Joris
authors.initials: J
authors.lastname: Vanderlocht
authors.forename: Ann
authors.initials: A
authors.lastname: Driessen
authors.forename: Adriaan P
authors.initials: AP
authors.lastname: de Bruïne
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Gassler
authors.forename: Wim G
authors.initials: WG
authors.lastname: van Gemert
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
mesh_terms: D000328:Adult; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006090:Gram-Negative Bacteria / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D007234:Infant, Premature; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism / Q000382:microbiology; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000378:metabolism*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4