The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online January 7, 2008
doi:10.1084/jem.20071022
The Journal of Experimental Medicine, Vol. 205, No. 1, 183-193
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Ménard et al.
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ARTICLE

Developmental switch of intestinal antimicrobial peptide expression

Sandrine Ménard1,3, Valentina Förster3, Michael Lotz2,3, Dominique Gütle3,4, Claudia U. Duerr3,4, Richard L. Gallo5, Birgitta Henriques-Normark1, Katrin Pütsep2, Mats Andersson2, Erik O. Glocker3, and Mathias W. Hornef1,3,4

1 Swedish Institute for Infectious Disease Control and 2 Microbiology and Tumor Biology Center, Karolinska Institute, 171 77 Stockholm, Sweden
3 Institute for Medical Microbiology and Hygiene, University of Freiburg, 79104 Freiburg, Germany
4 Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany
5 Medicine/Pediatrics, University of California, San Diego, San Diego, CA 92161

CORRESPONDENCE Mathias Hornef: hornef.mathias{at}mh-hannover.de

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.


Abbreviations used: CRAMP, cathelin-related antimicrobial peptide; CRS, cryptdin-related sequence; GBS, group B streptococci; Hprt1, hypoxanthine guanine phosphoribosyl transferase 1; IEC, intestinal epithelial cell; Mbd, mouse β-defensin; MMP, metalloproteinase; ZO-1, Zonula occludens protein 1.

S. Ménard's present adresses is Institut National de la Santé et de la Recherche Médicale, U793, Faculté Necker-Enfants-Malades, 75730 Paris, Cedex 15, France.

E. Glocker's present address is Royal Free and University College Medical School, London WC1E 6BT, England, UK.


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