Regional variations in Paneth cell antimicrobial peptide expression along the mouse intestinal tract

Jenny Karlsson, Katrin Pütsep, Hiutung Chu, Robert J. Kays, Charles L Bevins, Mats Andersson

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Background: Enteric antimicrobial peptides secreted from Paneth cells, including α-defensins (in mice named cryptdins), are key effector molecules of innate immunity in the small intestine. The importance of Paneth cells α-defensins emerged from studies of enteric bacterial infection in genetically modified mice, as well as from recent studies linking reduced levels of these α-defensins to Crohn's disease localized to the ileum. However, analysis of expression of Paneth cell α-defensins is incomplete. We therefore performed a comprehensive evaluation of the distribution of antimicrobial molecules along the mouse small intestinal tract to identify potential variations in regional expression. Results: In conventionally reared mice, the repertoire of Paneth cell antimicrobials differs between duodenum and ileum. In contrast to the uniform expression of most Paneth cell antimicrobials, both cryptdin 4 and cryptdin-related sequences (CRS) 4C peptides were expressed at progressively increasing amounts (101- and 104 -fold, respectively) comparing duodenum and ileum. In tissues other than the small intestine, expression of CRS peptides was noted in thymus and caecum. Most Paneth cell products were also produced in the small intestine of germ-free mice at levels similar to those in controls, however CRS4C and RegIIIγ had reduced levels in the former (3- and 8-fold, respectively). No significant changes in expression levels of Paneth cell antimicrobial peptides was observed after oral challenge with either Salmonella enterica serovar typhimurium or Listeria monocytogenes, supporting current notions on the constitutive nature of this defensive system. Conclusion: The repertoire of antimicrobial peptides changes along the small intestinal tract, and a subset of these molecules are up-regulated upon colonization, but not in response to enteric bacterial pathogens. The changes detected upon colonization suggest that Paneth cell antimicrobial peptides may play an important role in commensal microbial homeostasis, in addition to their proposed role in protection against infection. In addition, the differential expression of CRS4C along the small intestine suggests mechanisms of regulation that are distinct from other Paneth cell derived antimicrobial peptides.

Original languageEnglish (US)
Article number37
JournalBMC Immunology
Volume9
DOIs
StatePublished - Jul 17 2008

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Paneth Cells
Peptides
Defensins
Small Intestine
Ileum
Duodenum
Salmonella enterica
Listeria monocytogenes
Bacterial Infections
Innate Immunity
Crohn Disease
Thymus Gland
Homeostasis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Regional variations in Paneth cell antimicrobial peptide expression along the mouse intestinal tract. / Karlsson, Jenny; Pütsep, Katrin; Chu, Hiutung; Kays, Robert J.; Bevins, Charles L; Andersson, Mats.

In: BMC Immunology, Vol. 9, 37, 17.07.2008.

Research output: Contribution to journalArticle

Karlsson, Jenny ; Pütsep, Katrin ; Chu, Hiutung ; Kays, Robert J. ; Bevins, Charles L ; Andersson, Mats. / Regional variations in Paneth cell antimicrobial peptide expression along the mouse intestinal tract. In: BMC Immunology. 2008 ; Vol. 9.
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abstract = "Background: Enteric antimicrobial peptides secreted from Paneth cells, including α-defensins (in mice named cryptdins), are key effector molecules of innate immunity in the small intestine. The importance of Paneth cells α-defensins emerged from studies of enteric bacterial infection in genetically modified mice, as well as from recent studies linking reduced levels of these α-defensins to Crohn's disease localized to the ileum. However, analysis of expression of Paneth cell α-defensins is incomplete. We therefore performed a comprehensive evaluation of the distribution of antimicrobial molecules along the mouse small intestinal tract to identify potential variations in regional expression. Results: In conventionally reared mice, the repertoire of Paneth cell antimicrobials differs between duodenum and ileum. In contrast to the uniform expression of most Paneth cell antimicrobials, both cryptdin 4 and cryptdin-related sequences (CRS) 4C peptides were expressed at progressively increasing amounts (101- and 104 -fold, respectively) comparing duodenum and ileum. In tissues other than the small intestine, expression of CRS peptides was noted in thymus and caecum. Most Paneth cell products were also produced in the small intestine of germ-free mice at levels similar to those in controls, however CRS4C and RegIIIγ had reduced levels in the former (3- and 8-fold, respectively). No significant changes in expression levels of Paneth cell antimicrobial peptides was observed after oral challenge with either Salmonella enterica serovar typhimurium or Listeria monocytogenes, supporting current notions on the constitutive nature of this defensive system. Conclusion: The repertoire of antimicrobial peptides changes along the small intestinal tract, and a subset of these molecules are up-regulated upon colonization, but not in response to enteric bacterial pathogens. The changes detected upon colonization suggest that Paneth cell antimicrobial peptides may play an important role in commensal microbial homeostasis, in addition to their proposed role in protection against infection. In addition, the differential expression of CRS4C along the small intestine suggests mechanisms of regulation that are distinct from other Paneth cell derived antimicrobial peptides.",
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