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 journalArticle

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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

Fingerprint

Lipopolysaccharides
Paneth Cells
Necrotizing Enterocolitis
Ileum
Mucous Membrane
Epithelial Cells
Inflammatory Bowel Diseases
Premature Infants
Lymphocyte Antigen 96
Newborn Infant
Laser Capture Microdissection
Bacterial Antigens
Messenger RNA
Plasma Cells
Gram-Negative Bacteria
Reverse Transcription
Intestines
Homeostasis
Immunohistochemistry
Antigens

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Wolfs, T. G. A. M., Derikx, J. P. M., Hodin, C. M. I. M., Vanderlocht, J., Driessen, A., De Bruine, A. P., ... Buurman, W. A. (2010). Localization of the lipopolysaccharide recognition complex in the human healthy and inflamed premature and adult gut. Inflammatory Bowel Diseases, 16(1), 68-75. https://doi.org/10.1002/ibd.20995

Localization of the lipopolysaccharide recognition complex in the human healthy and inflamed premature and adult gut. / Wolfs, Tim G A M; Derikx, Joep P M; Hodin, Caroline M I M; Vanderlocht, Joris; Driessen, Ann; De Bruine, Adriaan P.; Bevins, Charles L; Lasitschka, Felix; Gassler, Nikolaus; Van Gemert, Wim G.; Buurman, Wim A.

In: Inflammatory Bowel Diseases, Vol. 16, No. 1, 02.2010, p. 68-75.

Research output: Contribution to journalArticle

Wolfs, TGAM, Derikx, JPM, Hodin, CMIM, Vanderlocht, J, Driessen, A, De Bruine, AP, Bevins, CL, Lasitschka, F, Gassler, N, Van Gemert, WG & Buurman, WA 2010, 'Localization of the lipopolysaccharide recognition complex in the human healthy and inflamed premature and adult gut', Inflammatory Bowel Diseases, vol. 16, no. 1, pp. 68-75. https://doi.org/10.1002/ibd.20995
Wolfs, Tim G A M ; Derikx, Joep P M ; Hodin, Caroline M I M ; Vanderlocht, Joris ; Driessen, Ann ; De Bruine, Adriaan P. ; Bevins, Charles L ; Lasitschka, Felix ; Gassler, Nikolaus ; Van Gemert, Wim G. ; Buurman, Wim A. / Localization of the lipopolysaccharide recognition complex in the human healthy and inflamed premature and adult gut. In: Inflammatory Bowel Diseases. 2010 ; Vol. 16, No. 1. pp. 68-75.
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